Systemic and cerebrospinal fluid T-helper cytokine responses in organ transplant recipients with Cryptococcus neoformans infection.

Nina Singh, Shahid Husain, Ajit P Limaye, Kenneth Pursell, Goran B Klintmalm, Timothy L Pruett, Jyoti Somani, Valentina Stosor, Ramon del Busto, Marilyn M Wagener, Chad Steele

Author Information

Nina Singh: University of Pittsburgh, Pittsburgh, PA, USA. nis5@pitt.edu

PMID: 16860707 DOI: 10.1016/j.trim.2006.03.009

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-gamma or IL-12 (Th1)/IL-10 (Th2) ratio < 1.0 was considered a dominant Th2 response.
RESULTS: Cases had lower ratios of IFN-gamma/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-gamma/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-gamma/IL-10 ratio of < 1.0 (p = 0.015). The levels of IL-10 (p = 0.04) and IFN-gamma (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.

R01 A1054719-01/PHS HHS

Cryptococcus neoformans

Cytokines

Female

Fungemia

Humans

Male

Meningitis, Cryptococcal

Organ Transplantation

Prospective Studies

Th1 Cells

Th2 Cells

Cytokines

Clinical Trial Comparative Study Journal Article Multicenter Study Research Support, N.I.H., Extramural

Antifungal management practices and evolution of infection in organ transplant recipients with cryptococcus neoformans infection.An immune reconstitution syndrome-like illness associated with Cryptococcus neoformans infection in organ transplant recipients.[Cryptococcus neoformans meningitis with normal cerebrospinal fluid].Cryptococcus neoformans in cerebrospinal fluid and blood.Cryptococcus neoformans infection in organ transplant recipients: variables influencing clinical characteristics and outcome.[Initial cerebrospinal fluid in Cryptococcus neoformans meningoencephalitis].Clinical significance of cytomegalovirus-specific T helper responses and cytokine production in lung transplant recipients.Cryptococcus neoformans in organ transplant recipients: impact of calcineurin-inhibitor agents on mortality.Unusual morphological forms of Cryptococcus neoformans in cerebrospinal fluid.identification of Cryptococcus neoformans in cytologic preparations of cerebrospinal fluid.

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