Comparison of the effects of recombinant interleukin 6 and recombinant interleukin 1 on nonspecific resistance to infection

Abstract

Interleukin 1 (IL 1) is a potent enhancer of nonspecific resistance to infection in mice. Since IL1 also induces interleukin 6 (IL6), we tested the hypothesis that IL 6 medi ates the effect of IL1 on nonspecific resistance. In a lethal Pseudomonas aeruginosa infection in granulocytopenic mice, in which 80 ng of recombinant human IL la pro tects against death, IL 6 appeared to be much less effective. Dosages of 8 ng, 80 ng and 320 ng IL 6 did not differ from the control, whereas 800 ng had a marginal protective effect (0.05 < p < 0.1). IL1 and IL 6 did not potentiate each other in ani mals treated with suboptimal dosages of both cytokines. Numbers of bacteria cultured from the blood, thigh muscle, liver, spleen, and kidney were similar in animals treated with 800 ng IL 6 and in control animals, arguing against activation of microbicidal mechanisms. The serum concentration profile of IL 6 after an i.p. injection of 80 ng IL1 was similar to that after 80 ng IL 6 i.p. Only minute amounts of IL1 were detected in serum after an i.p. injection of IL 6. Taken these data together, it appears that increased resistance to infection induced by IL1 is not mediated by IL 6.

Effects of recombinant human interleukin-6 alone and in combination with recombinant interleukin-1 alpha and tumor necrosis factor alpha on antibacterial resistance in mice

“…Although one might propose that these results were due to our using human IL-6 in mice, other investigators have reported that human IL-6 from the same source (Genetics Institute) stimulates an acute-phase response in mice (12). Our results are generally consistent with the observations of Van der Meer et al (16), who found that rIL-6 increased survival but did not increase bacterial clearance in granulocytopenic mice infected with P. aeruginosa. These authors also reported that rIL-6 did not potentiate the protection offered by IL-1 in their model.…”

“…To the best of our knowledge, there is no compelling published evidence for the protective effects of rIL-6 in experimental infection models. This is in contrast to the monokines rIL-1 and rTNF-a, which offer substantial protection against a variety of infectious agents when administered to experimental animals (3,14,16). Taken together, these findings suggest that, rather than being a major player in the protective host response to infection, IL-6 release represents an attempt by the host to repair tissue damage during microbial infection.…”

Role of acute-phase proteins in interleukin-1-induced nonspecific resistance to bacterial infections in mice

“…The deleterious effects of IL-6 in infections have also been suggested in several reports (31,36). We addressed this issue by administering higher doses of IL-6 prior toP.…”

Protective effects of interleukin-6 in lipopolysaccharide (LPS)-induced experimental endotoxemia are linked to alteration in hepatic anti-oxidant enzymes and endogenous cytokines

“…IL-6 knockout mice treated with LPS produce threefold more TNF-a than do their wild-type controls, suggesting that endogenous IL-6 may be important in the control of LPSinduced TNF-a synthesis (Cuzzocrea et al 1999). In addition, IL-6 was found to induce hypo responsiveness to endotoxin in mice and to inhibit the release of TNF-a in mouse ( Van der meer et al 1981). Evidence for anti-inflammatory role of IL-6 is derived from studies with rats in which administration of IL-6 was shown to reduce the acute neutrophil exudation caused by administration of LPS (Ulrich et al 1990).…”