Cytokine profiles of AIDS patients are similar to those of mice with disseminated Cryptococcus neoformans infection

Cryptococcosis is an hematogenously disseminated meningoencephalitis during which the relationship between the disease severity and the immune respons e remains unclear, Ne thus analyzed, by enzyme-linked immunosorbent assay, proinflammatory (tumor necrosis factor alpha [TNF-alpha] and interleukin-6 [IL-6]) and anti-inflammatory (IL-10) cytokine levels in plasma at the time of diagnosis in 51 AIDS patients with culture-proven en cryptococcosis, We used a murine model to determine the correlation between cytokine levels a nd fungal burden in blood and tissues and the kinetics of the immune respon se and of the formation of cerebral lesions. In AIDS patients, plasma TNF-a lpha and IL-10 but not IL-6, levels were significantly higher in the case o f fungemia or disseminated infection than in their absence, whereas the pre sence of meningitis had no influence on these levels. In mice, none of thes e cytokines were detected within the first day after inoculation. Later on, TNF-alpha and IL-10, but not IL-6, levers in plasma correlated significant ly with the fungal burden in the blood and spleen but not the brain. In the brain, cytokine levels were low compared to those in other compartments, a nd tissue lesions and a degree of infection similar to those observed in hu mans were seen, further suggesting the relevance of this experimental model . Thus, AIDS patients with cryptococcosis produce an immune response that r eflects the dissemination but not the meningeal involvement. This murine mo del of disseminated cryptococcosis can be used to investigate the pathophys iology of cryptococcosis and new therapeutic approaches.