Cytokine mRNA Expression in Pneumococcal Carriage, Pneumonia, and Sepsis in Young Mice

We studied cytokine mRNA expression in Streptococcus pneumoniae carriage, pneumonia, and sepsis in 3week-old, inbred C57BL/6 and BALB/c mice. Mice were inoculated intranasally with S. pneumoniae serotype 6B, 14, or 3. Survival, bacterial load in the nasopharynx (NP) and lungs, and mRNA levels of tumor necrosis factor (TNF)–a, transforming growth factor (TGF)–b, interleukin (IL)–10, and IL-12 in the spleen were analyzed. No baseline mRNA expression levels were found, except for TNF-a in C57BL/6 mice. Serotype 6B caused NP colonization only, a significant ( ) increase in the levels of TNF-a, and induction of TGF-b P ! .05 and IL-12 mRNA. Serotype 14 caused NP and nonlethal lung colonization and induction of TGF-b, IL-10, and IL-12. Serotype 3 caused NP colonization, pneumonia, 35% mortality, and no alteration in the mRNA expression of tested cytokines. Although activation of the immune system culminated in nonlethal disease, evasion of the immune system was associated with detrimental disease. Streptococcus pneumoniae is a leading cause of morbidity and mortality in infants and elderly persons. The incidence of invasive pneumococcal disease in children aged 0–2 and 3–4 years is 145 and 25 cases/100,000 persons, respectively, whereas, in older people (age 5–54 years), it is dramatically lower: 5 cases/100,000 persons, with an age-dependent increase: 15 cases/100,000 persons at age 55–64 years, 21 cases/100,000 persons at age 65–74 years, and 75 cases/100,000 persons at age 75 years [1]. The mammalian host defies infection through a combination of innate and adaptive immune responses. Innate immunity preexists in the host, acts within minutes of the interaction with the pathogen until the generation of adaptive response, and is composed of physical