Interleukin 1 receptor blockade attenuates the host inflammatory response.
Cytokines, including interleukin 1 (IL-1), tumor necrosis factor alpha, and interleukin 6, are often produced in response to tissue injury and contribute to several host responses such as weight loss, anorexia, and acute-phase protein synthesis. However, the role of IL-1 in specific tissue responses is unclear. To test our hypothesis that specific in vivo blockade of IL-1's action might inhibit the catabolic host changes associated with inflammation, mice were passively immunized with a monoclonal antibody directed against the murine IL-1 receptor prior to initiation of a turpentine-induced sterile abscess. This antibody prevents IL-1-mediated proliferation of murine thymocytes in vitro by inhibiting IL-1 alpha and IL-1 beta by way of competition for a common receptor. Weight loss following turpentine challenge was prevented by daily injections of anti-IL-1 receptor monoclonal IgG. Body composition analysis confirmed that lean tissue and fat were preserved by passive immunization. Furthermore, pretreatment with an anti-IL-1 receptor monoclonal antibody significantly attenuated the plasma amyloid P and interleukin 6 responses but did not affect the decline in plasma albumin or the increase in circulating corticosterone. Passive immunization of similar mice with polyclonal antisera against another cytokine, tumor necrosis factor alpha, failed to prevent either the weight loss or hepatic acute-phase protein changes observed in this inflammatory model. These findings suggest that IL-1 orchestrates weight loss and body compositional changes during inflammation and contributes to the induction of interleukin 6 and acute-phase protein synthesis.
Laboratory of Surgical Metabolism, Cornell University Medical College, New York, NY 10021.
J E
JE
Gershenwald
Y M
YM
Fong
T J
TJ
Fahey
S E
SE
Calvano
R
R
Chizzonite
P L
PL
Kilian
S F
SF
Lowry
L L
LL
Moldawer
D000209:Acute-Phase Proteins / Q000032:analysis; D000818:Animals; D000906:Antibodies; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D001066:Appetite; D001835:Body Weight; D003345:Corticosterone / Q000032:analysis; D005260:Female; D006400:Hematocrit; D007116:Immunization, Passive; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology*; D007375:Interleukin-1 / Q000276:immunology; D007958:Leukocyte Count; D008055:Lipids / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D011971:Receptors, Immunologic / Q000276:immunology*; D017472:Receptors, Interleukin-1; D012016:Reference Values; D014425:Turpentine
D000209:Acute-Phase Proteins; D000906:Antibodies; D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D008055:Lipids; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D003345:Corticosterone; D014425:Turpentine