Jaakko Uksila

No benefit of long‐term ciprofloxacin treatment in patients with reactive arthritis and undifferentiated oligoarthritis: A three‐month, multicenter, double‐blind, randomized, placebo‐controlled study

OBJECTIVE To investigate the effect of long-term antibiotic treatment in patients with reactive arthritis (ReA) and undifferentiated oligoarthritis. METHODS One hundred twenty-six patients were treated with ciprofloxacin (500 mg twice a day) or placebo for 3 months, in a double-blind, randomized study. Of these patients, 104 (48 treated with ciprofloxacin and 56 treated with placebo) were valid for clinical evaluation: 55 were diagnosed as having ReA with a preceding symptomatic urogenic or enteric infection and 49 as having undifferentiated oligoarthritis. These 2 groups were randomized separately. The triggering bacterium was sought by serology and/or culture. The percentage of patients in remission after 3 months of treatment was chosen as the primary efficacy parameter. RESULTS A triggering bacterium could be identified in 52 patients (50%): Chlamydia trachomatis in 13, Yersinia in 14, and Salmonella in 25. No patient was positive for Campylobacter jejuni or for Shigella. No difference in outcome was found between treatment with ciprofloxacin or placebo in the whole group or in subgroups of patients with ReA or undifferentiated oligoarthritis. No difference was seen in patients with a disease duration <3 months. Ciprofloxacin was not effective in Yersinia- or Salmonella-induced arthritis but seemed to be better than placebo in Chlamydia-induced arthritis. This difference was not significant, however, which might be due to the small sample size. CONCLUSION Long-term treatment of ReA with ciprofloxacin is not effective; however, it might be useful in the subgroup of patients who have Chlamydia-induced arthritis. This has to be proven in a bigger study focusing on patients with Chlamydia-induced arthritis.

Etiologic aspects of chronic urticaria

Background Urticaria is a common disease that is always a challenge to the dermatologist due to its evasive etiology.

Testicular immunosuppressive protein

Auto-, allo- and xenografts of various endocrine tissues survive for prolonged periods in the testicular interstitium. The reason for transplant survival outside the blood-testis barrier has been obscure. In the present paper we describe a high molecular weight (Mr = 130,000), heat- and pH-labile immunosuppressive factor with an isoelectric point of 6.3-7.3 in extracellular fluid collected from the rat testicular interstitium. The results show that the testicular immunosuppressive agent is not a steroid, but a protein. This testicular immunosuppressive protein may contribute to the immune privilege in the testicular interstitium.

Early dissemination of Borrelia burgdorferi without generalized symptoms in patients with erythema migrans

The diagnosis of erythema migrans (EM) is not always easy, and reports of culture‐ or PCR‐confirmed diagnosis as well as reports of EM with simultaneous disseminated disease are few. Characteristics and incidence of EM in addition to frequency of early dissemination of B. burgdorferi were studied in the archipelago of South‐Western Finland prospectively using questionnaires, skin biopsies and blood samples. Clinical EM was recognized in 82 patients (incidence 148/100000 inhabitants/year). Of skin biopsy samples, 35.5% were positive by PCR (the majority B. garinii), and 21.5% by cultivation (all B. garinii). Of blood samples, 3.8% were positive by PCR, and 7.7% by cultivation. Of the patients, 30.9% were seropositive at the first visit, and 52.9% 3 weeks later. Of the patients with laboratory confirmed diagnosis, the EM lesion was ring‐like in 31.8% and homogenous in 65.9%. Dissemination of B. burgdorferi, based on culture or PCR positivity of blood samples, was detected in 11.0% of the patients. The frequency of generalized symptoms was nearly the same in patients with as in those without dissemination (22.2% vs 27.4%). Only 21.4% of the patients with culture‐positive EM recalled a previous tick bite at the site of the EM lesion. We conclude that EM lesions are more often homogenous than ring‐like. B. burgdorferi may disseminate early without generalized symptoms.

Testis physiology relevant to immunoregulation

Intra-testicular transplants are placed in rodents into the large lymphatic sinusoids of the interstitial tissue of the testis. These sinusoids are filled with a protein-rich extracellular fluid that supplies all the requirements of the grafts until vascularization takes place. The testicular microvascular endothelium regulates transport of T lymphocytes and immunoglobulin G to the testis and may thus contribute to regulation of the immune system in this organ. Differences in the organization of the lymphatic drainage exist between species, but in every studied species lymphatic drainage from the testis leads to lymph nodes.

Antibacterial effects of human group IIA and group XIIA phospholipase A2 against Helicobacter pylori in vitro

Group IIA phospholipase A2 (PLA2‐IIA) is an enzyme which has important roles in inflammation and infection. Recently, a novel human secretory PLA2 called group XIIA PLA2 (PLA2‐XIIA) has been identified. Both PLA2‐IIA and PLA2‐XIIA are bactericidal against Gram‐positive bacteria like many other secretory PLA2s. However, PLA2‐XIIA is the only known PLA2 displaying significant bactericidal activity against the Gram‐negative bacterium Escherichia coli. We examined the antibacterial properties of recombinant human PLA2‐IIA and PLA2‐XIIA against Helicobacter pylori, a Gram‐negative bacterium, in vitro. PLA2‐IIA was not bactericidal against H. pylori, whereas PLA2‐XIIA effectively killed H. pylori at a concentration of 50 μg/ml but was not bactericidal at concentrations of 0.5 μg/ml and 5 μg/ml.

Peptic ulcer and Helicobacter pylori in patients with lichen planus.

The aetiology of lichen planus is unknown, but it is often connected with infections. In recent years peptic ulcer disease has also been closely linked with an infectious agent, Helicobacter pylori. A case-control study was conducted in 78 patients with lichen planus to find out a previous history of peptic ulcer disease, using a questionnaire and a medical record review. Patients were also asked about family history in first- and second-degree relatives. Fifty-seven patients with other skin diseases were interviewed as controls. The prevalence of H. pylori infection in patients with lichen planus was compared to that of 39 patients with other skin diseases and to the overall prevalence rates of H. pylori infection in Finland. Our findings are consistent with an approximately three-fold increased risk of peptic ulcer in patients with chronic/repeating lichen planus, when compared to the control patients (p = 0.04) and also to the overall peptic ulcer prevalence rates in Finland. Forty-one percent of the patients with chronic/repeating lichen planus had a first- or second-degree family member with a peptic ulcer, while the corresponding rate in the control group was only 12% (p=0.003). The prevalence of H. pylori infection in patients with chronic/repeating lichen planus and transient lichen planus was not significantly different from that in patients with other skin diseases.

Trans‐urocanic acid, a natural epidermal constituent, inhibits human natural killer cell activity in vitro

Abstract UV irradiation has been reported to influence NK cell function both in vitro and in vivo. Since urocanic acid may mediate UV‐induced immune modulation we tested the effect of trans‐ and cis‐urocanic acid (UCA) on the cylotoxic activity of human peripheral blood lymphocytes against the erythroleukemic target cell line K562 in vitro. Trans‐UCA was found to be a strong inhibitor of NK cell activity whereas cis‐UCA had no effect. Trans‐UCA also partially inhibited cytotoxic function of IL‐2‐activated NK cells and reduced IL‐2‐induced activation of NK cells. This is the first report describing trans‐UCA to be active, and cis‐UCA inactive, in regulating an immune function. In the skin, a decrease in epidermal trans‐urocanic acid concentration by UV radiation could produce a favorable milieu for NK cell activity, and thus counteract the impairment of antigen‐specific immune surveillance, induced by increased cis‐urocanic acid concentrations.

Expression of CD80 (B7/BB-1) and CD28 in human white blood cells treated with urocanic acid.

Urocanic acid (UCA) is formed in the epidermis where it accumulates to be converted fromtrans-tocis-UCA by ultraviolet (UV) radiation. The two isomers modulate immune functions in several experimental systems. In particular,cis-UCA has been shown to induce antigen-specific immune tolerance, but the molecular mechanism of this effect is unknown. The present investigation was instituted to disclose any effect of UCA isomers on the cellular expression of the costimulatory antigens CD80 (B7/BB-1) and CD28. CD80 expression was efficiently induced in monocytic (CD14+) cells by human interferon-γ, while CD28 levels on lymphocytes remained unchanged, as detected by flow cytometry. Neither UCA isomer showed any effect on the expression patterns of these costimulatory molecules. The results obtained suggest that the mode of action for epidermal UCA-induced tolerogenesis may not involve modulation of CD80 (B7/BB-1) or CD28 expression.

Activation of the immune system in the testis

The present concept for the mechanism of prolonged transplant survival in the testis suggests that lymphocyte activation is inhibited locally in this site by testicular products. As the testis produces several immunoregulatory factors, the behaviour of lymphocytes in the testis may depend on the net effect of all these factors on intralymphocytic events. In the present article, the extra- and intracellular events associated with lymphocyte activation are reviewed and the steps of lymphocyte activation which might be subject to interference by testicular factors are identified.