Recombinant human interleukin-10 attenuates TNFalpha production by porcine monocytes.
BACKGROUND
Human recombinant interleukin-10 (rhIL-10) has been found to inhibit endotoxin-induced production of several proinflammatory cytokines including tumor necrosis factor alpha (TNFalpha) from human monocytes. The exogenous therapeutic administration of rhIL-10 in acute and chronic hyperinflammatory conditions has been discussed. For none of the large animal species that have been used to study the role and effects of various mediators during septicemia, crossreactivity of rhIL-10 has been shown so far. Therefore, the aim of the present investigation was to evaluate the crossreactivity of rhIL-10 in a porcine model.


METHODS
To determine the effects of rhIL-10 on endotoxin-challenged porcine monocytes, we incubated porcine peripheral blood monocytes from five donors with three different concentrations of rhIL-10 (500 ng/ml, 1000 ng/ml and 2000 ng/ml, respectively) either simultaneously with, or two hours prior to lipopolysaccharide (LPS) administration.


RESULTS
As compared to incubation with LPS (1 microg/ml) alone, coincubation with LPS and rhIL-10 (500 ng/ml, 1000 ng/ml and 2000 ng/ml) (n = 5) for four hours resulted in a marked and uniform reduction of immunoreactive TNFalpha. For preincubation (n = 5), only the addition of 500 ng/ml rhIL-10 led to a homogeneous decrease of TNFalpha levels in each sample. There was no consistent reduction in TNFalpha after preincubation with 1000 and 2000 ng/ml rhIL-10. Our results indicate crossreactivity of recombinant human interleukin-10 in porcine peripheral blood monocytes. Further investigations on the potential therapeutical role of exogenously administered rhIL-10 are thus possible in porcine models.
Hofstetter
C
C
Institute of Anesthesiology, Klinikum Grosshadern, University of Munich, Marchioninistr. 15, D-81366 Munich, Germany.
Kleen
M
M
Habler
O
O
Allmeling
A M
AM
Krombach
F
F
Zwissler
B
B
D000276:Adjuvants, Immunologic / Q000378:metabolism; D000818:Animals; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis*
D000276:Adjuvants, Immunologic; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10