Details

Autor(en) / Beteiligte

• Jos W. M. Van Der Meer
• Barza, Michael
• Wolff, Sheldon M.
• Dinarello, Charles A.

Titel

A Low Dose of Recombinant Interleukin 1 Protects Granulocytopenic Mice from Lethal Gram-Negative Infection

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 1988-03, Vol.85 (5), p.1620-1623

Ort / Verlag

Washington, DC: National Academy of Sciences of the United States of America

Erscheinungsjahr

1988

Quelle

MEDLINE

Beschreibungen/Notizen

• Natural and synthetic immunomodulators that increase nonspecific resistance to infection induce interleukin 1 (IL-1) production. Therefore, we investigated the effect of the administration of IL-1 on the survival of lethally infected granulocytopenic mice. Mice with cyclophosphamideinduced granulocytopenia were injected with approximately 107 Pseudomonas aeruginosa in the thigh muscle at time O; gentamicin was administered 6 hr and 23 hr later. When recombinant human IL-1β (one of the two forms of IL-1) was given as a single i.p. injection 24 hr before the infection, survival was increased. Using 80 ng of IL-1β per mouse, survival compared to control animals was 98% vs. 71% at 24 hr, 98% vs. 60% at 30 hr, 86% vs. 36% at 36 hr, and 61% vs. 11% at 48 hr (P<0.001) after the infection. No effect of IL-1 was observed when it was given 0.5 hr before or 6 hr after the infection. Animals not treated with gentamicin also benefited from the IL-1. Administration of the cyclooxygenase inhibitor ibuprofen did not affect the activity of IL-1. Numbers of bacteria cultured from the blood, thigh muscle, liver, spleen, and kidney were similar in IL-1-treated and control animals. Superoxide production by peritoneal macrophages was also similar in the two groups. These studies demonstrate that IL-1 pretreatment protects granulocytopenic mice against lethal pseudomonas infection and suggest that this protection occurs through a noncellular mechanism.