TREATMENT WITH ANTI-INTERLEUKIN-10 MONOCLONAL-ANTIBODY ENHANCES EARLYRESISTANCE TO BUT IMPAIRS COMPLETE CLEARANCE OF LISTERIA-MONOCYTOGENES INFECTION IN MICE

Mice that received an anti-interleukin-10 (anti-IL-10) neutralizing mo noclonal antibody (MAb) (SXC-1) prior to infection with Listeria monoc ytogenes initially demonstrated resistance to the infection, as indica ted by reduced recovery of L. monocytogenes from their spleens and liv ers during the first 5 days after challenge. Anti-IL-10 MAb-treated mi ce then demonstrated reduced resistance during the later stage of infe ction, as indicated by persistent infection with L. monocytogenes in t heir livers 11 days after challenge. Aspartate aminotransferase (AST) levels (a measure of liver damage) in the sera of control mice increas ed between 1 and 5 days after challenge, while anti-IL-10 MAb-treated mice maintained lower AST levels. At 7 days after challenge, AST level s in the sera of control mice decreased as the numbers of organisms de clined. In contrast, AST levels increased as the infections persisted in anti-IL-10 MAb-treated mice. The AST levels in serum reflected live r histopathology as anti-IL-10 MAb-treated mice exhibited fewer granul omatous lesions and less necrosis of liver tissue than the control mic e during the first 5 days after challenge. Anti-IL-10 MAb treatment al tered the expression of inflammatory cytokine mRNAs during L. monocyto genes infection. Control MAb-treated mice exhibited increased expressi on of tumor necrosis factor alpha and granulocyte-macrophage colony-st imulating factor mRNA in their livers during L. monocytogenes infectio n, but this increase did not occur in anti-IL-10 MAb-treated mice. Gam ma interferon mRNA expression in the livers of the control MAb-treated mice was increased between 1 and 5 days after L. monocytogenes challe nge and then decreased at 7 days after challenge. In contrast, gamma i nterferon mRNA expression in the livers of anti-IL-10 MAb-treated mice was not decreased until 7 days after challenge. These results indicat e that endogenous IL-10 has both beneficial and detrimental effects on the host response to L. monocytogenes infection in mice.