Interleukin-10 attenuates the release of proinflammatory cytokines but depresses splenocyte functions in murine endotoxemia.
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.


METHODS
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.
Ertel
W
W
Department of Surgery, University of Zurich, Switzerland.
Keel
M
M
Steckholzer
U
U
Ungethüm
U
U
Trentz
O
O
D000818:Animals; D003602:Cytotoxicity, Immunologic; D004731:Endotoxins / Q000097:blood*; D004926:Escherichia coli; D007111:Immunity, Cellular; D016753:Interleukin-10 / Q000502:physiology*; D007378:Interleukins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D013154:Spleen / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D004731:Endotoxins; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10