Differential interleukin-10 and gamma interferon mRNA expression in lungs of cilium-associated respiratory bacillus-infected mice

The cilium-associated respiratory (CAR) bacillus is a gram-negative, extrac ellular bacterium that causes persistent respiratory tract infections in ro dents. We have previously demonstrated that BALB/c mice are more susceptibl e to CAR bacillus-induced disease than resistant C57BL/6 mice, with elevati ons in pulmonary gamma interferon (IFN-gamma) and interleukin (IL)-4. IL-10 is a type 2 cytokine that can increase host susceptibility to bacterial di seases through its anti-inflammatory effects, including suppression of macr ophage function. The purpose of this study was to further describe the cyto kine profiles associated with histologic lesions in CAR bacillus-infected m ice and to assess the effects of cytokine depletion on the pathogenesis of disease. Six-week-old female BALB/c and C57BL/6 mice and mice with targeted mutations in IFN-gamma and IL-4 were inoculated intratracheally with 10(5) CAR bacillus organisms, and samples were collected at 6 to 7 weeks postino culation. Lung samples were collected for histopathologic examination and a nalysis of cytokine mRNA. IFN-gamma, IL-10, and IL-4 mRNA levels in the lun gs of infected mice were semiquantitatively measured using a reverse transc riptase-mediated PCR assay and compared to those in uninfected control anim als of each strain. BALB/c mice infected with CAR bacillus had a median lun g lesion score of 6 and IL-10 and IL-4 mRNA levels were significantly eleva ted. The majority of C57BL/6 mice were resistant to disease characterized b y lung lesions scores of 2 or less and a dominant IFN-gamma mRNA cytokine p rofile. A few C57BL/6 mice with lesions scores of 5 or greater had elevatio ns in all three cytokines and were susceptible to disease. C57BL/6 IFN-gamm a knockout mice had increased disease with elevations in IL-10 and IL-4 mRN A, while BALB/c IL-4 knockout mice infected with CAR bacillus had a mild de crease in lesion severity and an attenuated IL-10 mRNA expression compared to wild-type BALB/c mice. These data indicate that IL-10 and IL-4 predomina te in CAR bacillus-induced histologic lesions in mice, while IFN-gamma, may play a role in resistance to disease.