PubMed Health⌕ Search

Biomedical subjects

K D Chavin

Publications and source records attributed to K D Chavin.

43 records · Page 3Linked to original sources
PubMed1991

Inhibition of macrophage-activating cytokines is beneficial in the acute septic response.

Interferon-gamma and other cytokines enhance macrophage (M phi) antimicrobial function and have been considered for therapeutic use in sepsis. Systemic sequelae of macrophage activation, however, are unclear. This study examined the effects of M phi activating cytokines (interferon-gamma [IFN-gamma] and interleukin-4 [IL-4]) and monoclonal antibodies directed against these cytokines in modulating the acute septic response. CFW/Swiss Webster mice (n = 345) received endotoxin (lipopolysaccharide [LPS]: 60 mg/kg body weight intraperitoneally) and were randomized to five treatment groups: IFN-gamma (10(4) units), IL-4 (10(4) units), IgG1 isotype antibody (TRFK5: 200 micrograms), anti-IFN-gamma (200 micrograms), or anti-IL-4 (200 micrograms) monoclonal antibodies (MAbs) given simultaneously or 2 hours after LPS. Animals were divided into two groups and studied for mortality or measurement of peritoneal M phi superoxide anion release (O2-), tumor necrosis factor (TNF), and IL-6 production 6 hours after administration of LPS +/- experimental regimens. Serum TNF and IL-6 also were assessed at 2 and 4 hours after LPS, respectively. Administration of LPS resulted in a 27% survival compared with 10% in the IFN-gamma and 13% in the IL-4 groups. Treatment with anti-IFN-gamma offered protection against LPS lethality (93%-100% survival, p less than 0.001 vs. other groups) when given either simultaneously or 2 hours after LPS. Anti-IFN-gamma also significantly decreased PM phi O-2 and TNF release. Thus anti-IFN-gamma may have an important role in the modulation of the acute septic response.

Acute Disease↗
PubMed1991

Anti-CD2 monoclonal antibodies alter cell-mediated immunity in vivo.

The antimurine CD2 mAb 12-15 was administered intravenously to investigate the role of CD2 in cell-mediated immunity in vivo. The anti-CD2 mAb was able to diminish the contact sensitivity response to the hapten trinitrophenyl and was most effective when administered during the efferent or elicitative phase of immunity. Antibody treatment was also able to inhibit in vivo priming for subsequent generation of secondary, TNP-specific CTL in vitro. This inhibitory effect was most effective in the afferent or early phase of immunity. Indeed antibody could be injected at least 3 weeks prior to in vivo antigen priming, and the subsequent CTL response was still suppressed. Additional experiments showed a well-defined dose-response relationship between the amount of anti-CD2 administered and subsequent immunosuppression. Control experiments showed that other isotype-matched antibodies were not suppressive and that the anti-CD2 was not merely shifting the kinetics of the CTL response. Further experiments revealed that in vivo mAb treatment could also inhibit the subsequent development of primary, alloantigen-specific CTL in vitro while the mixed lymphocyte reaction (MLR) remained unchanged. FACS analysis revealed a marked downmodulation of CD2 in vivo, a small and variable decrease in CD8, and essentially no change in CD3 or CD4 after treatment with anti-CD2. The F(ab')2 fragment was not able to downmodulate CD2 or to suppress CTL activity at the doses tested. These results support a major role for CD2 in diverse aspects of cell-mediated immunity affecting both CD4+ and CD8+ effector T cells. The anti-CD2 mAb functions not by deleting or depleting relevant cell populations but rather by altering the array of cell surface receptors and subsequent responses to antigenic challenge.

Animals↗
PubMed1991

Adrenal suppression and steroid supplementation in renal transplant recipients.

The use of increased dosages of glucocorticoids during periods of physiologic stress in allograft recipients represents a clinical dilemma in that the short-term exogenous therapy required may significantly impair wound healing and immunocompetence. To investigate whether "stress steroids" are actually necessary, a prospective study was conducted in 40 renal allograft recipients admitted with significant physiologic stress. Stress categories included sepsis, metabolic abnormalities, and surgery. These patients received only their baseline prednisone immunosuppression (5-10 mg/day) and no supraphysiologic or stress doses of glucocorticoids. The clinical course of the patients revealed no evidence of adrenal insufficiency. There was no mortality, increase in hospital stay, or eosinophilia. Five episodes of hyponatremia and seven instances of hypotension were attributed to primary disease processes and responded promptly to specific treatment without steroid supplementation. Biochemical evaluation during stress revealed suppression of ACTH levels in 74.5% of episodes, elevation of urinary free cortisol levels in 79.1% of episodes, and elevation of isolated serum cortisol levels in 55.9% of episodes. This suggested that these patients had physiologically adequate adrenal function. The cosyntropin stimulation test overestimated the incidence and degree of clinically significant adrenal dysfunction (63% of patients) and was not a useful indication of a requirement for additional glucocorticoids. We conclude that functional adrenal suppression is uncommon in renal allograft recipients receiving baseline prednisone immunosuppression (5-10 mg/day) and that the demands of physiologic stress are met by a combination of endogenous adrenal function plus exogenous, baseline, immunosuppressive doses of glucocorticoids. Supra-physiologic or high doses of so-called "stress steroids" are not required. The cosyntropin stimulation test has significant clinical limitations and did not serve to alter clinical care.

Adrenal Glands↗
PubMed1988

Decreased Epstein-Barr virus-induced transformation, and elevated 2-5A synthetase and RNase L activity in peripheral blood mononuclear cells from patients treated with recombinant interferon alfa 2b.

Patients with cutaneous T-cell lymphoma (CTCL) were treated with recombinant alfa 2b interferon (rIFN alfa 2b) by intramuscular injection. Therapy-induced changes in Epstein-Barr virus (EBV) induced transformation of patient peripheral blood lymphocytes, 2',5' oligoadenylate (2-5A) synthetase levels and RNase L activation in peripheral blood mononuclear cells were monitored. Inhibition of EBV-induced transformation and elevation of 2-5A synthetase levels correlated with increased activation of RNase L, which provides evidence that intramuscular administration of rIFN alfa 2b induces a sustained anti-EBV state in CTCL patient peripheral blood mononuclear cells which can be detected in vitro.

2',5'-Oligoadenylate Synthetase↗