Open Access

ARTICLE

Interleukin-1 receptor antagonist transiently impairs antibacterial defense but not survival in murine pneumococcal pneumonia

Anita W. Rijneveld^1,2,*, Sandrine Florquin³, Peter Speelman^2,4, Carl K. Edwards⁵, Charles A. Dinarello⁶, Tom van der Poll^2,4

Academic Medical Center, University of Amsterdam, the Netherlands; Departments of 1 Experimental Internal Medicine, 2 Internal Medicine, 3 Pathology, 4 Infectious Diseases, Tropical Medicine and AIDS, 5 Amgen, Incorporated, Thousand Oaks, California 91320, 6 University of Colorado Health Sciences Center, Denver, Colorado 80262

* Corresponding Author: Anita W. Rijneveld,

European Cytokine Network 2003, 14(4), 242-245.

Abstract

The inhibition of the biological activity of IL-1 by recombinant human IL-1 receptor antagonist (IL-1ra) has been investigated in several, controlled clinical trials. Encouraging results have been reported, in particular in patients with rheumatoid arthritis. In the present study, we investigated the influence of treatment of wild type mice with IL-1ra, which resulted in an incomplete and transient inhibition of IL-1 activity. Treatment with recombinant human IL-1ra resulted in an enhanced bacterial outgrowth in the lungs of BALB/c and C57BL/6 mice early after induction of pneumococcal pneumonia, without influencing survival or the pulmonary inflammatory response. The effect of IL-1ra on the host response to S. pneumoniae pneumonia is modest and transient. The present data, together with the findings in IL-1R−/− mice in earlier work, suggest that IL-1 occupies a role in the pulmonary immune response to S. pneumoniae that is substantially less prominent than that of TNF-α.

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