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Abstract: Background: The role of Th1 and Th2 mediated cytokine responses in the pathogenesis of Cryptococcus neoformans infection in organ transplant recipients has not been defined. Methods: We assessed cytokine levels in the sera and CSF collected prospectively at the time of diagnosis of infection in 25 transplant recipients with cryptococcosis. Serum levels were compared with those in healthy individuals and transplant recipients without cryptococcosis. IFN-γ or IL-12 (Th1)/IL-10 (Th2) ratio <1.0 was considered a dominant Th2 response. Results: Cases had lower ratios of IFN-γ/IL-10 (p =0.03) and IL-12/IL-10 (p =0.03) compared to healthy individuals. Cytokine responses, however, did not differ significantly for cases vs. transplant controls. Cases with fungemia compared to those without fungemia tended to have higher serum IL-10 levels (p =0.07) and lower IL-12/IL-10 ratios (p =0.06). CSF ratios of IFN-γ/IL-10 (p =0.04) and IL-12/IL-10 (p =0.04) were lower in cases with cryptococcal meningitis compared to those without meningitis; 80% (8/10) of the cases with cryptococcal meningitis vs. 0% (4/4) of those without meningitis had CSF IFN-γ/IL-10 ratio of <1.0 (p =0.015). The levels of IL-10 (p =0.04) and IFN-γ (p =0.04) in the CSF in cases with cryptococcal meningitis were significantly higher than those in their serum, respectively. Conclusions: High expression of Th2 phenotype in cryptococcal meningitis and in fungemia suggests that Th dysregulation may contribute to the pathogenesis of cryptococcosis in organ transplant recipients. [Copyright &y& Elsevier]