The role of the spleen in the protective effect of C-reactive protein in Streptococcus pneumoniae infection.

C-reactive protein (CRP) is an acute phase serum protein in man which activates complement and has opsonic activity. We have reported that prior injection of CRP into mice can increase their survival following intravenous challenge with Streptococcus pneumoniae type 3 or 4. In this study the conditions required for protection, and the role of hepatic and splenic clearance of bacteria have been examined. Protection against lethal infection was observed with a minimum dose of 25-50 micrograms CRP per mouse. CRP was most effective when administered between 6 h before and 2 h after challenge. CRP treated mice were not protected against infection with Salmonella typhimurium, LT-2, an organism which does not bind CRP. Mice depleted of C3 by treatment with cobra venom factor were protected against S. pneumoniae infection by CRP. Pre-treatment of mice with CRP did not increase the rate of clearance of viable S. pneumoniae from the bloodstream but did increase splenic and decrease hepatic clearance of radiolabelled bacteria in both normal and complement depleted mice. Although these findings suggest a role for the spleen in CRP protection, mice which had been splenectomized were also protected against lethal pneumococcal infection by CRP treatment.