Donna L. Vredevoe

Beta Blocker and Angiotensin-Converting Enzyme Inhibitor Therapy Is Associated with Decreased Th1/Th2 Cytokine Ratios and Inflammatory Cytokine Production in Patients with Chronic Heart Failure

Objective: To examine the potential impact of β-blockers and angiotensin-converting enzyme (ACE) inhibitors, medications which modulate β-adrenergic signaling, on immune function in patients with chronic heart failure (HF). Methods: 118 patients attending an HF center were tested for circulating levels of norepinephrine (NE), T cells and the inflammation-associated cytokine interleukin 6 (IL-6). Levels of the cytokines interferon-γ (IFNγ), IL-10, and tumor necrosis factor-α (TNFα) produced by cultured peripheral blood mononuclear cells (PBMC) were measured in culture supernatants following T cell stimulation in vitro. Results: NE levels were significantly lower in patients receiving ACE inhibitors (p = 0.0263), with a trend toward lower NE in patients receiving β-blockers. All patients exhibited relatively normal levels of T cells, and there was a trend toward higher levels of total (CD3+) and helper (CD4+) T cells (p = 0.0578 and 0.0932, respectively) in patients receiving either type of medication. The ratios of Th1 (IFNγ) to Th2 (IL-10) cytokines were lower in patients receiving a combination of β-blocker and ACE inhibitor therapy (p = 0.0373). NYHA class was a significant predictor of serum IL-6 (p < 0.0001). There was a trend toward lower levels of serum IL-6 in patients receiving both types of medications (p = 0.0606). TNFα production by CD3/CD28-stimulated PBMC was significantly lower in patients receiving ACE inhibitor medications (p = 0.0223). Conclusions: These results suggest that high sympathetic tone associated with chronic HF affects Th1/Th2 and inflammatory cytokine production, and that these effects can be modulated by medications. In addition to improvement in clinical parameters relating to cardiovascular function, β-blocker and ACE inhibitor medications also appear to have a beneficial effect on the immune system in HF.

Natural Killer Cell Anergy to Cytokine Stimulants in a Subgroup of Patients with Heart Failure: Relationship to Norepinephrine

Heart failure is a disease characterized by chronically high levels of plasma norepinephrine and anergy in the cytotoxicity of circulating natural killer (NK) lymphocytes. This study shows that NK anergy extends to a significantly reduced cytotoxicity in response to the powerful NK stimulants, interleukin (IL)-2 and interferon (IFN)-alpha. Fifteen patients with heart failure, New York Heart Association stage III or IV, were studied for NK-cell-mediated cytotoxicity. The patients were divided into two groups based upon their NK cytotoxicity function: (1) those who had minimal baseline cytotoxicity and failed to respond following stimulation by IL-2 and IFN-alpha (n = 6), and (2) those who were about at the level of normal controls, and were responsive to IL-2 and IFN-alpha (n = 9). There was no relationship between the anergy and the etiology of the heart failure, laboratory indicators of heart failure, serum albumin or sodium, state anxiety, age or sex of the subjects. There was a statistically significant negative correlation between the response of NK cells to the stimulators IL-2 and IFN-alpha and the level of plasma norepinephrine in the heart failure patients. This was corroborated by in vitro testing of direct effects of norepinephrine on normal NK cells, which indicated that baseline cytotoxicity and the ability of these cells to respond to IL-2 were inhibited in a dose-dependent manner. The findings indicate that the NK cell anergy seen in heart failure patients extends to the response to the stimulators IL-2 and IFN-alpha in a subgroup of patients.

Relation of depression, natural killer cell function, and infections after coronary artery bypass in women.

Background: After hospital discharge for coronary artery bypass grafting (CABG), infection is a common cause of morbidity. Although depression has been associated with immune dysfunction, its role in post-CABG infection is unknown. Aims: The purpose of this study was to: 1) compare natural killer cell cytotoxicity (NKCC) and post-hospitalization infections in depressed and non-depressed women after CABG; and 2) test whether NKCC mediated the relationship between post-discharge depression and infections. Methods: Sixty-seven women recovering from CABG were assessed for depression prior to hospital discharge and followed for six months. Major depression was identified by a structured clinical interview. Infections were identified by patient report using the Modified Health Review and by medical chart audit. Results: Compared to non-depressed women after CABG, women with major depression had reduced NKCC, more all-cause infections, and more self-reported illnesses. Although NKCC did not mediate the relationship between depression and wound (i.e. incisional) infections after CABG, it did mediate the relationship between depression and non-wound infections, including pneumonias and upper respiratory infections. Conclusions: For the first six months after CABG, women with major depression are at increased risk for infections. Natural killer cell cytotoxicity may be related to this phenomenon, particularly to non-wound infections.

Monokine Production Following in Vitro Stimulation of the THP-1 Human Monocytic Cell Line with Pertussis Vaccine Components

Whole-cell pertussis found in diphtheria–tetanus–pertussis (DTP) vaccine can produce symptoms reminiscent of biological responses to circulating proinflammatory monokines such as IL-6, IL-1β, and TNFα. Therefore the ability of pertussis-containing vaccines and several heat-killed Bordetella pertussis preparations to stimulate cytokine production in a human monocytic cell line, THP-1, were examined. The whole-cell pertussis vaccine induced significantly more IL-6, IL-1β, and TNFα production than did the acellular pertussis or diphtheria–tetanus-only vaccine. Polymyxin B was able to inhibit most of the IL-6 induced by pertussis endotoxin and a heat-killed preparation of B. pertussis containing a null mutation in bvgAS, a regulatory locus required for expression of all known protein virulence factors synthesized by this organism. However, it only partially inhibited IL-6 production induced by other pertussis-containing preparations, including DTP vaccine. These results indicate that in vitro whole-cell vaccine is a potent stimulator of IL-6, IL-1β, and TNFα. They also suggest that although endotoxin is a major inducer of IL-6, other components of B. pertussis also contribute to IL-6 production by monocytes.

Recovery of the murine mononuclear phagocytic system following chronic exposure to cadmium

Consistent with our previously reported findings, chronic ingestion of cadmium chloride in drinking water by mice caused a decrease in the rate of circulation clearance of 51Cr-labeled sheep red blood cells (E) and IgG-coated E (E-IgG) due to a decrease in the localization of E and E-IgG in the liver. These decreases reached their nadirs after 15 weeks of cadmium ingestion and remained relatively constant for up to one year during continued ingestion of cadmium. Replacement of the drinking water containing cadmium with regular tap water resulted within 8 days in an improvement in the ability of the mice to clear E and E-IgG. Mice also had a decreased ability to develop delayed-type hypersensitivity reactions while being given cadmium; this abnormality also returned toward normal after withdrawal of cadmium. The return of these two responses toward control levels occurred while there was still a large organ burden of cadmium that was not measurably different from that at cessation of cadmium ingestion.

Circulating Small Lymphocytes: Immunologically Competent Cells with Limited Reactivities

Highly purified small lymphocytes from peripheral blood are capable of producing acute transplantation disease. However, such lymphocytes do not transfer from sensitized to normal mice the capacity to produce antibody to bovine serum albumin under conditions where mixed populations of lymphoid cells from the sensitized donors are effective.

Allergy as a risk factor for nursing care problems in the elderly cancer patient.

The purpose of this secondary analysis was to determine (a) the nursing diagnoses in elderly patients with cancer and (b) whether elderly cancer patients with a current or past history of allergy were at risk for selected nursing problems. A retrospective clinical data base from 59 patients (32 male, 27 female) with a diagnosis of cancer and an age range of 55–85 years with a mean age of 65.6 years was examined. The most frequently occurring priority nursing diagnoses identified by Clinical Nurse Specialists (CNS) were Pain, Risk for Infection, and Impairment of Skin Integrity. When examining the comprehensive list of priority and nonpriority nursing diagnoses, identified for these patients with cancer, it was found that those with a history of allergy were significantly more likely to have a high risk for infection than those without a history of allergy. Two other diagnoses (knowledge deficit and potential fluid volume deficit) occurred in a significant number in the allergy group, but there was no occurrence of these two diagnoses in the nonallergy group. The limitations of assessing immunologic status as a part of regular nursing assessments were discussed. Recommendations were provided for future research in the area of immunology, aging, and nursing diagnoses.

Predictors of natural killer cell-mediated cytotoxicity deficiency in advanced heart failure secondary to either ischemic or idiopathic dilated cardiomyopathy

The effect of psychologic variables (situational emotional state and psychiatric diagnosis) and physiologic variables (plasma norepinephrine, decreased cardiac exercise capacity, and elevated pulmonary capillary wedge pressure) on natural killer cell activity was evaluated in 19 patients with advanced heart failure of ischemic or idiopathic origin. Only peak exercise capacity was independently predictive of natural killer cell deficiency.