Interleukin-10 attenuates the release of proinflammatory cytokines but depresses splenocyte functions in murine endotoxemia
W. Ertel, M. Keel, U. Steckholzer, U. Ungethum and O. Trentz
Department of Surgery, University of Zurich, Switzerland.
OBJECTIVE: To determine whether interleukin (IL)-10, besides its potent
anti-inflammatory properties, causes depression of splenocyte functions in
a murine model of gram-negative endotoxemia. DESIGN: Mice (strain C3H/HeN)
were injected intravenously with 1 mg of Escherichia coli
lipopolysaccharide at 15 minutes after intravenous injection of either 200
U of recombinant murine IL-10 or saline solution. Serum levels of tumor
necrosis factor alpha, IL-6, and IL-1 alpha were determined at 90 minutes
and 12 hours after lipopolysaccharide challenge. In addition, splenocyte
proliferation and lymphokine release (IL-2, IL-6, and interferon gamma)
were measured. RESULTS: Pretreatment with IL-10 markedly reduced (P <
.05) serum levels of tumor necrosis factor alpha (-79%), IL-6 (-94%), and
IL-1 alpha (-69%), but it significantly inhibited splenocyte proliferation
(-32%) and IL-2 (-40%), IL-6 (-49%), and interferon gamma (-54%) release of
splenocytes. CONCLUSIONS: Interleukin-10 prevents E coli
lipopolysaccharide-induced cytokinemia but dampens antigen-driven cellular
immune responses. Although IL-10 protects against the detrimental effects
of proinflammatory cytokines by deactivation of macrophages, its
immunosuppressive effect may augment susceptibility to repeated or
continuous invasion of microorganisms, as it is observed during clinical
sepsis.
