Takae Kawamura

Elevation of cytokines during open heart surgery with cardiopulmonary bypass : participation of interleukin 8 and 6 in reperfusion injury

Myocardial ischaemia is one of the major causes of low output syndrome during open heart surgery. Injury associated with ischaemia and reperfusion has been considered to result, in part, from the action of neutrophils, the interaction of neutrophils with vascular endothelial cells, and the effects of cytokines which are mediators that induce and modify reactions between these substances. We investigated cell injury in relation to the concentrations of interleukins 6 and 8 (IL-6 and IL-8), which have recently received attention as neutrophil activators. Neutrophil counts, granulocyte elastase (GEL), IL-6, IL-8, tumour necrosis factor-α (TNF-α), CK, and CK-MB concentrations were determined serially in 11 patients undergoing open heart surgery with cardiopulmonary bypass (CPB). Neutrophil counts (mean ±SD 2717 ±2421 μl−1 preoperatively) peaked 60 min after declamping the aorta at 7432 ±4357 μl−1 (P < 0.01) and remained elevated 7136 ±5194 μl−1 at 180 min (P < 0.01). Plasma GEL level (168 ±71 μg sd L−1 preoperatively) peaked at 1134 ±453 μg · L−1 120 min after declamping of the aorta (P < 0.01) and remained elevated, 1062 ±467 μg · L−1, after 180 min (P < 0.01). Serum IL-6 level (118 ±59 pg · ml−1 preoperatively) peaked at 436 ±143 pg · ml−1 60 min after declamping of the aorta (P < 0.01) and remained elevated, 332 ±109 pg · ml−1, after 180 min. Serum IL-8 level (37 ±44 pg · ml−1 preoperatively) peaked at 169 ±86 pg · ml−1 at 60 min after declamping of the aorta (P < 0.001) and remained elevated at 113 ±78 pg · ml−1 180 min after declamping of the aorta. Serum TNF-α was decreased at 60 min after aortic occlusion but otherwise did not change. Plasma GEL concentrations correlated with serum IL-8 levels (R = 0.7, P = 0.001) and the IL-6 and IL-8 concentrations correlated with the duration of aortic clamping (R = 0.64, P = 0.01, R = 0.7, P = 0.01). We conclude that the increases of IL-6 and IL-8 occur as a result of ischaemia, and suggest that these cytokines participate in reperfusion injury by activating neutrophils.RésuméL’ischémie myocardique est une des principales causes du syndrome de bas débit pendant la chirurgie à coeur ouvert. On pense que la lésion associée à l’ischémie et la reperfusion résulte en partie de l’action des neutrophiles, l’interaction des neutrophiles avec les cellules vasculaires endothéliales et l’activité de médiateurs, les cytokines qui induisent et modifient les réactions entre ces substances. Nous avons examiné la relation de la lésion cellulaire avec la concentration des interleukines 6 et 8 (IL-6 et IL-8), qui ont récemment attiré l’attention comme activateurs de neutrophiles. Chez 11 patients soumis à une chirurgie cardiaque ouverte avec circulation extracorporelle (CEC), on mesure en série le décompte des neutrophiles, l’élastase granulocytaire (GEL), l’IL-6 et l’IL-8, le facteur-α. de nécrose tumorale (TNF-α) et la concentration des CK et CK-MB. Le décompte des neutrophiles (moyenne ±SD: 2717 ±2421 μl−1 en préopératoire) atteint un maximum de 7432 ±435 μl−1 60 min après le déclampage de l’aorte (P < 0,01) et demeure élevé, 7136 ±5194 μl−1, à 180 min (P < 0,01). Le niveau de la GEL plasmatique (168 ±71 μg · L−1 en préopératoire) atteint un maximum de 1134 ±453 μg · L−1 après 120 min du déclampage de l’aorte (P < 0,01) et demeure élevé, 1062 ±467 μg · L−1 après 180 min de déclampage (P < 0,01). L’IL-6 sérique (118 ±59 pg · ml−1) atteint un maximum de 436 ±143 pg · ml−1 60 minutes après le déclampage de l’aorte (P < 0,01) et demeure élevé, 332 ±109 pg · ml−1 après 180 min. Le niveau sérique d’IL-8 (37 ±44 pg · ml−1 en préopératoire) atteint un maximum de 169 ±86 pg · ml−1 60 min après le déclampage de l’aorte (P < 0,01) et demeure élevé, 113 ±78 pg · ml−1 après 180 min. Le TNF-α décroît 60 min après le clampage aortique mais ne change plus par la suite. La concentration plasmatique de GEL est en corrélation avec le niveau sérique de l’IL-8 (R = 0,7, P = 0,001). Les concentrations d’IL-6 et d’IL-8 sont en corrélation avec la durée du clampage (R = 0,64, P = 0,01, R = 0,07, P = 0,01). Nous concluons que les augmentations d’IL-6 et d’IL-8 résultent de l’ischémie et nous suggérons qu’en activant les neutrophiles, ces cytokines participent à la genèse de la lésion de reperfusion.

Influence of methylprednisolone on cytokine balance during cardiac surgery

OBJECTIVE To determine the influence of methylprednisolone on the cytokine balance during cardiac surgery. DESIGN Prospective, randomized, nonblinded study. SETTING University hospital. PATIENTS Twenty-one patients on cardiopulmonary bypass undergoing aortocoronary bypass surgery. INTERVENTIONS According to a randomized sequence, the patients either received methylprednisolone (30 mg/kg) [corrected] before cardiopulmonary bypass and before declamping of the aorta (MPS group, n = 11) or received nothing (control group, n = 10). MEASUREMENTS AND MAIN RESULTS Serum proinflammatory cytokines (interleukin [IL]-8, IL-6) and anti-inflammatory cytokines (IL-10, IL-1ra) were measured by enzyme-linked immunosorbent assays. Serum IL-6 and IL-8 concentrations in the control group (15.2 +/- 4.1 and 14.1 +/- 1.9 pg/mL, preoperatively) increased to 242 +/- 70.1 and 97.3 +/- 18.3 pg/mL at 60 mins after declamping of the aorta (p < .01, p < .01, respectively). The increases were greater than those from 2.5 +/- 0.6 and 2.5 +/- 0.5 pg/mL to 109.5 +/- 29.0 and 33 +/- 4.1 pg/mL in the MPS group for IL-6 and IL-8, respectively. Serum IL-10 concentrations increased significantly 60 mins after declamping of the aorta compared with its preoperative value in the two groups (the control group, from 1.0 +/- 0 to 537.9 +/- 61.7 pg/mL; the MPS group, from 0.3 +/- 0.2 to 654.9 +/- 24 pg/mL [p < .01, p < .01, respectively]). No difference was found between the two groups. Similarly, serum IL-1ra concentrations in the two groups increased the preoperative value in the control group from 304 +/- 120 to 44,374 +/- 14,631 pg/mL and in the MPS group from 616.5 +/- 109.6 to 35,598 +/- 9,074 pg/mL at 60 mins after declamping of the aorta (p < .01, p < .01, respectively). There was no difference between the two groups. CONCLUSIONS Methylprednisolone reduces the production of IL-6 and IL-8 but not that of IL-10 and IL-1ra. These results suggest that one of the mechanisms of the cytoprotective effect of methylprednisolone may be to make changes in the proinflammatory and anti-inflammatory cytokine balance.

Methylprednisolone inhibits increase of interleukin 8 and 6 during open heart surgery

It has been reported that interleukin 8 (IL-8) and interleukin 6 (IL-6) are two of the chemical mediators causing myocardial injury. It is not clear whether treatment with corticosteroids in vitro in these patients can prevent the production of interleukin 8 and 6. This prospective study was conducted to investigate whether methylprednisolone (MP) pretreatment (30 mg · kg−1 before CPB and before declamping of aorta) influenced the production of IL-8 and 6 in the peripheral circulation in 27 patients undergoing elective coronary artery bypass surgery. The IL-8 and IL-6 concentrations were measured by ELISA kit. We also studied the effect of MP pretreatment on postoperative cardiac Junction. Serum concentration of IL-8 in non-MP-treated patients (37 ± 44 pg · ml−1 preoperatively) increased to 169 ± 86 pg · ml−1 60 min after declamping of the aorta (P < 0.001). The increase was greater than the increase from 22 ± 8.9 pg · ml−1 to 52 ± 35 pg · ml−1 in the MP-treated patients (P < 0.01). Serum IL-6 concentration in non-MP-treated patients increased from the preoperative value of 59 ± 30 pg · ml−1 to 436 ± 143 pg · ml−1 60 min after declamping of the aorta (P < 0.001). The increase was greater than the increase from 36 ± 15 pg · ml−1 to 135 ± 55 pg · ml−1 in the MP-treated patients (P < 0.01). Furthermore, postoperative cardiac index in MP-treated patients (3.6 ± 1.1 L · min−1· m−2) was higher than 2.3 ± 0.8 L · min−1 · m−2 of non MP-treated patients (P < 0.05). The levels of IL-8 max during surgery correlated negatively with postoperative cardiac index (γ = −0.67). These results suggest that methylprednisolone suppresses production of IL-8 and 6.RésuméOn a rapporté que l’interleukine 8 (IL-8) et que l’interleukine 6 (IL-6) étaient deux des médiateurs chimiques de la lésion cardiaque. Toutefois, on ne sait pas encore si le traitement aux corticostéroïdes in vivo prévient la production des interleukines 8 et 6. Cette étude prospective vise à déterminer si le prétraitement à la méthylprednisolone (MP) (30 mg · kg−1 avant le CEC et avant le déclampage de l’aorte) influence la concentration de l’IL-8 de l’IL-6 du sang veineux périphérique de 27 patients soumis à une chirurgie réglée de revascularisation myocardique. Les concentrations de l’IL-8 de l’IL-6 sont mesurée avec une trousse Elisa. Nous étudions aussi les répercussions du traitement à la MP sur la fonction cardiaque postopératoire. La concentration sérique de l’IL-8 des patients non traités (37 ± 44 pg · ml−1 en préopératoire) augmente à 169 ± 86 pg · ml−1 60 minutes après le déclampage de l’aorte (P < 0,001). Cette augmentation est plus importante que l’augmentation de 22 ± 8,9 pg · ml−1 à 52 ± 55 pg · ml−1 notée chez les patients traité à la MP (P < 0,01). La concentration serique de l’IL-6 chez les patients non traités à la MP augmente de la valeur préopératoire de 59 ± 30 pg · ml−1 à 436 ± 143 pg · ml−1 60 min après le déclampage de l’aorte (P < 0,001). Cette augmentation est plus importante que celle de 36 ± 15 pg · ml−1 à 135 ± 55 pg · ml−1 survenue chez les patients traités à la MP (P < 0,01). De plus, l’index cardiaque postopératoire des patients traités à la MP (3,6 ± 1,1 L · ml−1 · m−2) est plus élevé que celui des patients non traités 2,3 ± 0,8 L · ml−1 · m− 2 (P < 0,05). Les niveaux maximaux de 1’IL-8 sont en corrélation négative avec l’index cardiaque postopératoire (y = 0,67). Ces resultats suggèrent que la méthylprednisolone supprime la production de l’IL-8 et de l’IL-6.

Hepatic blood flow and function in elderly patients undergoing laparoscopic cholecystectomy.

Laparoscopic cholecystectomy (LC) has been widely accepted as an alternative to laparotomy and has many advantages, including short hospital stay and very limited surgical invasion. However, this procedure may impair hepatic function in elderly patients because high pressure is maintained in the peritoneal cavity for an extended period. We observed the effect of pneumoperitoneum on the middle hepatic venous blood flow (MHVBF) in elderly patients undergoing LC. LC patients were anesthesized with inhaled and epidural anesthesia, after which MHVBF was continuously measured by transesophageal echocardiography. MHVBF decreased significantly during a period of high intraperitoneal pressure, and recovery of MHVBF after deflation was significantly lower in elderly patients (65–75 yr), but not in younger patients (24–62 yr). In contrast, MHVBF remained almost constant in elderly patients during open cholecystectomy, and thus was significantly different from that in patients who underwent LC with pneumoperitoneum. Laparoscopic cholecystectomy may impair hepatic function in elderly patients because high pressure is maintained in the peritoneal cavity for an extended period. Implications We observed the effect of pneumoperitoneum on the middle hepatic venous blood flow by transesophageal echocardiography and liver function in elderly patients undergoing laparoscopic cholecystectomy. Laparoscopic cholecystectomy may impair hepatic function in elderly patients because high pressure is maintained in the peritoneal cavity for an extended period.

Prostaglandin E1 reduces myocardial reperfusion injury by inhibiting proinflammatory cytokines production during cardiac surgery.

Objective To determine the influence of prostaglandin E1 (PGE1) on the cytokine balance and myocardial protection during cardiac surgery. Design Prospective, randomized, nonblinded study. Setting University hospital. Patients A total of 19 patients on cardiopulmonary bypass undergoing cardiac surgery. Interventions According to randomized sequence, the patients received PGE1 (0.02∼0.05 &mgr;g·kg−1·min−1) from the beginning of surgery to the end of study (PGE1 group, n = 11) or nothing (control group, n = 8). Measurements and Main Results Interleukin (IL)-6, IL-8, IL-10, IL-1 receptor antagonist (IL-1ra), soluble tumor necrosis factor receptor I (sTNF RI), and soluble tumor necrosis factor receptor II (sTNF RII) were measured by enzyme-linked immunosorbent assays. Troponin-T and isoenzyme of creatine kinase with muscle and brain subunits (CK-MB) were measured by enzyme immunoassay and ultraviolet absorption spectrophotometry method, respectively. Serum IL-6 and IL-8 concentrations in both groups increased significantly from 60 mins after declamping the aorta compared with preoperative value (p < .001), However, the increases were greater in the control group than in the PGE1 group (p < .01). Serum IL-10, IL-1ra, sTNF RI, and sTNF RII concentrations increased significantly from 60 mins after declamping the aorta compared with preoperative values in two groups (p < .001, respectively). There were no differences between the two groups. Serum troponin T and CK-MB concentrations increased significantly in the two groups from 60 mins after declamping the aorta (p < .001), but these increases were greater in the control group than in the PGE1 group (p < .01). IL-6 and IL-8 levels correlated with CK-MB concentration (r2 = 0.49, r2 = 0.36;p > .001 respectively). Conclusions PGE1 suppressed the production of IL-6 and IL-8 but not IL-10, IL-1ra, sTNF RI, or sTNF RII. The change in the balance between pro-and anti-inflammatory cytokines may be one of the most important cytoprotective mechanisms of PGE1.

Interleukin-10 and interleukin-1 receptor antagonists increase during cardiac surgery

BackgroundIt has been reported that inflammatory cytokines such as interleukin-8 and 6 (IL-8, IL-6) increase during cardiac surgery and cause postoperative cardiac dysfunction. Therefore, it is important to investigate changes of suppressive cytokines such as IL-10, interleukin-4 (IL-4) and interleukin-1 receptor antagonist (IL-1 ra) dunng cardiac surgery.MethodSerum levels of cytokines and IL-1 ra were measured in 10 patients during cardiac surgery with cardiopulmonary bypass. Six blood samples were drawn after inducing anaesthesia. In each sample, serum IL-10, IL-4, IL-8, IL-6 and IL-1 ra were measured by enzyme linked immunosorbent assay.ResultsSerum IL-6 and IL-8 concentration (19.1 ±8.8 pg · ml−1, and 13.4±5.2 pg · ml−1, preoperatively) increased to 227.5± 191 pg · ml−1 and 81.0±56 pg · ml−1 at 60 min after declamping the aorta (P< 0.01, respectively). Serum IL-10 concentration increased at 60 min after dedamping the aorta compared with the preoperative value (from 1.0±0 pg · ml−1 to 552.0± 158 pg · ml−1 P< 0.001]). Similarly, serum IL-1 ra concentration increased from the preoperative value of 1331±896 pg · ml−1 to 43353±12812 pg · ml−1 at 60 min after dedamping the aorta (P< 0.00l). Positive correlations were obtained between IL-10 and IL-8. and between IL-10 and IL-6 (γ=0.7, γ=0.8, P< 0.001, respectively).ConclusionThese findings demonstrate that pro-and anti-inflammatory cytokines increase to maintain their balance during cardiac surgery.RésuméObjectifOn a rapporté que la concentration des cytokines de l’inflammation comme les interleukines 6 et 8 (IL-8. IL-6) s’élevaient pendant la chirurgie cardiaque et provoquaient des dérangements cardiaques postopératoires. II est donc aussi important d’examiner les perturbations produites par les cytokines suppressives comme IL-10, interleukine-4 (IL-4) et de l’antagoniste du récepteur de l’interleukine-1 (IL-1 ra) pendant la chirurgie cardiaque.MéthodesLa concentration sérique des cytokines et de IL-1 ra a été mesurée chez dix patients pendant une chirurgie cardiaque sous CEC. Six échantillons de sang ont été prélevés après l’induction de l’anesthésie. Dans chacun des échantillons. on a titré IL-10, IL-4, IL-8, IL-6 et IL-1 ra avec l’épreuve de l’immuno-absorption enzymatique.RésultatsLes concentrations de IL-6 et de IL-8 (valeurs préopératoires : 19, 1 ±8, 8 pg · ml−1 et 13.4±5.2 pg · ml−1) ont augmenté à 227,45±191 pg · ml−1 et 81, 0±56 pg · ml−1 60 min après le dédampage de l’aorte (respectivement P< 0, 01 ). La concentration sérique de IL-10 a augmenté 60 min après le dédampage de l’aorte comparativement aux valeurs préopératoires (de 1.0±0 pg · ml−1 à 552± 158 pg · ml−1, P < 0.001). De la même façon, la concentration sérique de IL-1 ra a augmenté de la valeur préopératoire de 1331 ±896 pg · ml−1 à 4 3353± 1 2812 pg · ml−1 60 min après le dédampage (P < 0,001). La corrélation était positive entre IL-10 et IL-8 et entre IL-10 et IL-6 (respectivement γ=0.7, γ=0.8, P < 0,001).ConclusionCes données montrent que les cytokines pro- et anti-inflammatoires augmentent pour maintenir leur équilibre pendant la chirurgie cardiaque.

Nicorandil attenuates NF-kappaB activation, adhesion molecule expression, and cytokine production in patients with coronary artery bypass surgery.

Nicorandil (NCR), a KATP channel opener, has been reported to preserve microvascular integrity in patients with reperfused myocardial infarction. We tested the hypothesis that NCR suppresses myocardial ischemia and reperfusion injury via the attenuation of cytokine production. Forty patients who underwent coronary artery bypass graft surgery were studied. The patients were randomly divided into two groups, i.e., the patients with NCR (4-6 mg/h; N group, n = 20) or without NCR (C group, n = 20). Cardiac surgery was performed under anesthesia using fentanyl and propofol. Blood were sampled at the time of induction of anesthesia, pre-cardiopulmonary bypass, 60 min after aortic occlusion, and 60, 120, and 180 min after declamping the aorta. The activation of NF-κB, expression of adhesion molecules, and cytokine production were evaluated in blood samples from the control volunteers by flow cytometric analysis with or without lipopolysaccharide (LPS) stimulation in vitro. Serum IL-6 and IL-8 levels in both groups increased 60 min after declamping the aorta compared with the preoperative value (P < 0.001); the increases of these parameters in N group were lower than those in C group (P < 0.05). Serum creatine kinase with muscle and brain subunits and troponin-T levels increased 60 min after declamping the aorta in two groups (P < 0,001), but the increases of both parameters in N group were lower than those in C group (P < 0.05). NF-κB activation, CD11b/CD18 expression, and the production of TNF-α, IL-8, and IL-6 in monocytes and granulocytes were inhibited by NCR in vitro. NCR suppressed the increase of inflammatory cytokines such as IL-6 and IL-8 levels, and reduced myocardial reperfusion injury. The inhibition on NF-κB activation, adhesion molecule expression, and cytokine production may be one of the important mechanisms of myocardial protection of NCR.

Ulinastatin reduces elevation of cytokines and soluble adhesion molecules during cardiac surgery

PurposeTo investigate whether ulinastatin pretreatment (6000 U · kg−1 before CPB and before declamping of aorta) influenced the production of cytokines and adhesion molecules in the peripheral circulation.MethodsThis prospective randomized study was performed in 22 patients undergoing cardiac surgery. They were divided into two groups. Patients in Group I were untreated and in Group II treated with ulinastatin. The soluble intercellular adhesion molecule-1 (S-ICAM-1), soluble endothelial leukocyte adhesion molecule-1 (S-ELAM-1), interleukin8 and 6 (IL-8, 6) were measured using ELISA kits.ResultsSerum S-ICAM-1 concentration in Group I increased from the preoperative value of 297 ± 27 ng · kg−1 to 418 ± 106 ng · kg−1 at 60 min after declamping of the aorta (P < 0.01) but did not change in Group II. Serum S-ELAM-1 concentration did not change in either group. Serum concentration of IL-8 and IL-6 in Group I (37 ± 44 pg · kg−1, and 59 ± 59 pg · kg−1, preoperatively) increased to 169 ± 86 pg · kg−1 and 436 ± 143 pg · kg−1 at 60 min after declamping of the aorta (P < 0.001, P < 0.001). The increases were greater than those from 25 ± 6 pg · kg−1 and 30 ± 26 pg · kg−1 to 56 ± 36 pg · kg−1 and 132 ± 78 pg · kg−1 in Group II (P < 0.001, P < 0.001). The levels of S-ICAM-1 correlated with those of IL-8 (r = 0.5, P < 0.001).ConclusionThese results suggest that ulinastatin may suppress the increase in IL-8 production and the expression of ICAM-1 during cardiac surgery.RésuméObjectifRechercher si le l’administration préalable d’ulinastatin (6000 U · kg−1 avant la CEC et au déclampage de l’aorte) influençait la production de cytokines et de molécules adhésives dans la circulation périphérique.MéthodesCette étude prospective et aléatoire a été réalisée chez 22 patients soumis à une chirurgie cardiaque. Ils ont été répartis entre deux groupes. Les patients du groupe I n’ont pas reçu de l’ulinastatin alors que le groupe en a reçu. La molécule-1 adhésive intercellulaire soluble (S-1CAM-1), la molécule-1 endothéliale leucocytaire soluble (S-ALAM-1), les inlerleukines 8 et 6 (IL-8, 6) ont été mesurées à l’aide d’une trousse ELISA.RésultatsLa concentration sérique de S-ICAM-1 du groupe I a augmenté 60 min après le déclampage de l’aorte de la valeur préopératoire de 297 ± 27 ng · kg−1 à 418 ± 106 ng · kg−1 (P < 0,01) mais est demeurée inchangée dans le groupe II. La concentration sérique de IL-8 et IL-6 n’a pas changé dans les deux groupes. Les concentrations sériques de IL-8 et IL-6 dans le groupe I (valeurs préopératoires 37 ± 44 pg · kg−1 et 59 ± 59 pg · kg−1) ont a augmenté à 169 ± 86 pg · kg−1 et 436 ± 43 pg · kg−1 60 min après le déclampage de l’aorte (P < 0,001, P < 0,001). Les niveaux de S-ICAM-1 étaient en corrélation avec ceux de IL-8 (r = 0,5, P < 0,001).ConclusionCes résultats suggèrent que l’ulinastatin peut supprimer l’augmentation de la production de IL-8 et se ICAM-1.

Elevation of serum interleukin‐1 receptor antagonist levels in women with gynaecological cancers

This study included 15 patients with gynaecological cancers (7 with cervical cancer, 6 with endometrial cancer, and 12 with ovarian cancer); 7 with benign gynaecological disorders (5 with benign ovarian tumour and 2 with uterine myoma); and 10 healthy women as a control group. Serum interleukin‐1 receptor antagonist (IL‐1 ra) levels in patients with gynaecological cancer were significantly higher than those in patients with benign gynaecological disorders (P= 0.04) and in healthy controls (P= 0.0009). IL‐1 ra may play an important role in host immune responses in local and general environments against gynaecological cancers.

Interleukin-4, interleukin-10, and soluble tumor necrosis factor receptors in cord blood.

OBJECTIVE We assessed cord blood for levels of interleukin-4 (IL-4), interleukin-10 (IL-10), and p55 (sTNFR-I) and p75 (sTNFR-II) soluble tumor necrosis factor receptors. STUDY DESIGN Umbilical cord IL-4, IL-10, tumor necrosis factor alpha (TNF alpha), sTNFR-I, and sTNFR-II were measured in 21 normal appropriately grown newborns delivered vaginally (normal pregnancy), and 3 abnormal pregnancies (1 preterm delivery, 1 premature rupture of membranes with chorioamnionitis, and 1 abruptio placentae with fetal and neonatal distress). Umbilical cord arterial blood pH and PO2 were also measured. RESULTS The TNF alpha, sTNFR-I, and sTNFR-II were detectable in all cord blood samples in normal pregnancies. IL-4 was detected in 10 of 21 samples (47.6%), and IL-10 was undetectable in normal pregnancies. IL-10 could be detected in the cases with chorioamnionitis and abruptio placentae. Soluble tumor necrosis factor receptors in the case with preterm delivery and the case with abruptio placentae were elevated compared with the levels in control samples. CONCLUSION Both the p55 and p75 soluble tumor necrosis factor receptors are physiologic constituents of term cord blood. An immunosuppressive role of IL-10 and a protective role of soluble tumor necrosis factor receptors are suggested in abnormal pregnancies. However, in view of the small number of abnormal pregnancies, these observations must be considered preliminary.