IMPORTANCE OF INTERLEUKIN-10 IN GENETIC SUSCEPTIBILITY OF MICE TO COCCIDIOIDES-IMMITIS

Inbred strains of mice vary in their susceptibility to Coccidioides im miis, We infected resistant DBA/2 (D2) mice and three susceptible stra ins of mice (C57BL/6 [B6], BALB/c, and CAST/Ei) by intraperitoneal inj ection of arthroconidia and determined the severity of infection based on colony counts of fungus in the spleens and lungs 14 days after inf ection, We used quantitative reverse transcription-PCR to measure the amounts of cytokines made in the spleens and lungs of infected mice. S usceptible mice made 1,000-fold more interleukin-10 (IL-10) than resis tant D2 mice and about 10-fold more IL-4. In contrast, D2 mice had mor e IL-12 p40 in their lungs than did B6 mice. Resistant and susceptible mice made equivalent amounts of gamma interferon, IL-6, and IL-2, In order to determine whether IL-10 adversely affected the response to C. immitis, we infected IL-10-deficient mice, and they were found to be as resistant as D2 mice. This result indicates that IL-10 plays a cruc ial role in determining susceptibility to C, immitis in inbred mice, B ecause IL-4 mRNA levels were higher in most strains of susceptible mic e, we also infected IL-4-deficient B6 mice, They were more resistant t han B6 controls but not as resistant as IL-10-deficient mice, Thus, bo th IL-10 and IL-4 adversely affect the ability of C57BL mice to resist infection with C. immitis, but IL-10 has a larger effect and is the c ytokine that is consistently associated with susceptibility in all str ains of inbred mice.