The roles of IL-1, IL-6, and TNFalpha in the feeding responses to endotoxin and influenza virus infection in mice.
Influenza infection or administration of bacterial endotoxin (lipopolysaccharide, LPS) results in diminished feeding and loss of body weight. It has been suggested that these effects may be mediated by cytokines, such as interleukin-1 (IL-1), interleukin-6 (IL-6), and/or tumor necrosis factor-alpha (TNFalpha). To assess the potential role of these cytokines, we tested the ability of the naturally occurring IL-1-receptor antagonist (IL-1ra), a monoclonal antibody to mouse IL-6 (IL-6mAb), and a TNF binding protein fragment (TNFbp) to antagonize hypophagia induced by intraperitoneally (ip) injected mouse IL-1beta or LPS or by inoculation with influenza virus. Feeding was assessed by measuring the daily intake of food pellets and sweetened milk in a 30-min period. The hypophagia induced by mIL-1beta or LPS was not affected by pretreatment with IL-6mAb. The effects of IL-1beta were blocked by IL-1ra but unaffected by TNFbp. TNFbp and IL-1ra given separately both exhibited a tendency to attenuate LPS-induced hypophagia. The effectiveness of TNFbp plus IL-1ra treatment was similar to that of the individual antagonists. However, combined treatment with TNFbp, IL-1ra, and IL-6mAb almost completely prevented the depressing effect of LPS on milk intake. The antagonists were also tested in influenza virus-inoculated mice. IL-1ra was delivered chronically by osmotic minipumps and was supplemented by treatment with TNFbp and IL-6mAb. The treatments slightly attenuated the effects of the virus on milk intake 48 h after the inoculation and delayed the decrease in body weight. However, over the entire course of the experiment, the treatment produced very small, statistically nonsignificant, attenuations of the depressions in milk and food pellet intake. Similar results were obtained with TNFbp alone or the combination of IL-6mAb and TNFbp. The results suggest that IL-1beta, TNFalpha, and IL-6 contribute to the hypophagia induced by LPS. However, antagonism of all three cytokines was not sufficient to prevent the decreases in feeding and loss of body weight induced by influenza virus infection.
Swiergiel
A H
AH
Department of Pharmacology and Therapeutics, Louisiana State University Medical Center, Shreveport, Louisiana 71103, USA.
Dunn
A J
AJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018501:Antirheumatic Agents / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008124:Locomotion / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008892:Milk; D009976:Orthomyxoviridae Infections / Q000178:diet therapy / Q000276:immunology*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D047888:Receptors, Tumor Necrosis Factor, Type I; D012795:Sialoglycoproteins / Q000494:pharmacology; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology*
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D012795:Sialoglycoproteins; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha; C069521:recombinant human tumor necrosis factor-binding protein-1