In vivo anti inflammatory effects of the M20 IL-1 Inhibitor: I. Effects on acute inflammatory parameters

Abstract

Previous studies have described an IL-1 Inhibitor produced by a myelomonocytic line developed in our laboratory (Eur J Immunol 1986; 16: 1449). This IL-1 Inhibitor was secreted by the M20 line constitutively in addition to IL-1, from which it could be separated. We have recently shown that the M20 IL-1 Inhibitor is distinct from the IL-1ra. In vitro this factor inhibited IL-1 induced proliferative responses as well as PGE2 secretion by IL-1 induced fibroblasts. We also showed for the first time (Lymphokine Research 1988; 7(3): 268) that an IL-1 inhibitor can reduce IL-1 induced inflammatory effects. This study describes the specific effect of the M20 IL-1 Inhibitor on IL-1 induced parameters of inflammation: fever, leukocytosis and local foot pad swelling or lymph node enlargement. Purified preparations of the IL-1 Inhibitor, when injected together with IL-1, or before the IL-1, reduced fever, leukocytosis, foot pad swelling and lymph node enlargement caused by IL-1. Similar responses were obtained by injection of IL-6 or TNF, but were unaffected by the IL-1 Inhibitor, when injected together. These results indicate that the M20 IL-1 Inhibitor acts specifically on IL-1 induced responses in vivo. The potential importance of this factor as an anti-inflammatory and immune regulatory factor, is supported by the findings of this study.

In vivo anti-inflammatory effects of the M20 IL-1 Inhibitor: II. Effects on serum reactants

“…Again, the IL-1 Inhibitor reversed this effect of IL-1, but not of IL-6 nor TNF. The specificity of the M20 Inhibitor to IL-1 was reported in vitro [15,19] and in vivo [21,22,23] and is also clear from this additional in vivo study. Additionally, we have shown that this Inhibitor effects proliferation (but not differentiation) of normal and leukemic blood cells [30].…”

“…In the first part of this study [23], we showed that IL-1 induced fever, leukocytosis and local inflammation, as measured by foot pad swelling and lymph node enlargement. These were all reduced significantly by the M20 IL-1 Inhibitor.…”

“…We have recently shown that the M20 IL-1 Inhibitor prevents the onset of rheumatoid arthritis and reduces its severity in a rat model [22]. In the first part of this study [23] we described in detail the in vivo effects of this IL-1 Inhibitor upon IL-1 induced fever, leukocytosis and local inflammation.…”