Comparison of cytokine plasma levels in human African trypanosomiasis David Courtin 1 , Vincent Jamonneau 2 , Jean-Franc¸ois Mathieu 3 , Mathurin Koffi 4 , Jacqueline Milet 5 , Claude Sese Yeminanga 6 , Victor Kande Betu Kumeso 4 , Ge´rard Cuny 2 , Constantin Miaka Mia Bilengue 5 and Andre´ Garcia 6 1 Institut de Recherche pour le De´veloppement, Sante´ de la me`re et de l’enfant en milieu tropical, Paris, France 2 Institut de Recherche pour le De´veloppement, Interactions hoˆ tes-vecteurs-parasites dans les trypanosomoses, Montpellier, France 3 Becton Dickinson Biosciences, Le-Pont-de-Claix, France 4 Programme National de Lutte contre la Trypanosomiase Humaine Africaine, Kinshasa, Re´publique De´mocratique du Congo 5 Ministe`re de la Sante´, Kinshasa, Re´publique De´mocratique du Congo 6 Institut de Recherche pour le De´veloppement, Sante´ de la me`re et de l’enfant en milieu tropical, Cotonou, Benin Summary background Immunological studies suggest that human African trypanosomiasis (HAT) is associated with inflammatory responses. A better understanding of the complex cytokine interactions regulating HAT infections is essential to elucidate the mechanisms of generalized immunosuppression. method We determined levels of interleukin (IL)-2, IL-4, IL-6, IL-10, tumour necrosis factor (TNF)-a and interferon (IFN)-c protein levels in plasma samples from three groups of individuals from the Democratic Republic of Congo: (i) HAT cases; (ii) seropositive individuals for whom parasite detection was negative and (ii) controls. results Plasma levels of six cytokines were significantly higher in HAT cases than in both controls (P < 0.003) and seropositive individuals (P < 0.016). IL-2 and IL-10 concentrations were significantly lower (P < 0.02) in the seropositive group than in the control one. conclusion Human African trypanosomiasis leads to the development of strong cytokine responses, indicating the potential involvement of IL-2 and IL-10 in the phenomenon of seropositivity without parasitological confirmation. This strongly suggests the involvement of immunity in this particular aspect of HAT epidemiology. keywords gamma interferon, human African trypanosomiasis, interleukin, Trypanosoma brucei gambiense, tumour necrosis factor-alpha Introduction Human African trypanosomiasis (HAT) in West Africa is caused by Trypanosoma brucei gambiense (Tbg). Tbg HAT is classically described as a chronic form: after infection, trypanosomes proliferate in blood and lymph during the early stage, which is followed by a meningo-encephalitic or late stage characterized by cerebrospinal fluid invasion and central nervous system disorders (Buguet et al. 2001). The duration of the early stage can be up to several years, and the appearance of neurological disorders during the late stage often progresses rapidly. As for numerous infectious diseases, clinical presenta- tions and evolutions can strongly differ from the classical ones. Concerning Tbg HAT, acute (Truc et al. 1997) and asymptomatic (Jamonneau et al. 2000, 2004)forms have been described. Both the infectious agent and host immunity could play a role in this variability (Garcia et al. 2000; Jamonneau et al. 2004; Courtin et al. 2006). A particular attention has been paid for people positive to card agglutination test for trypanosomiasis (CATT) (Magnus et al. 1978), for which no parasite can be detected (Kanmogne et al. 1996; Simo et al. 1999). In a longitudinal follow-up, Garcia et al. (2000) confirmed that some of these individuals have probably been infected by Tbg, and the complete absence of disease after 32 months could be due to a strongly suited immune response. The purpose of the present preliminary study was to compare interleukin (IL)-2, IL-4, IL-6, IL-10, tumour necrosis factor (TNF)-a and interferon (IFN)-c protein levels in plasma samples between HAT cases, seropositive apparently aparasitemic subjects, and controls in order to explore the possible role of human immunity in this complex phenomenon. Tropical Medicine and International Health doi:10.1111/j.1365-3156.2006.01612.x volume 11 no 5 pp 647–653 may 2006 ª 2006 Blackwell Publishing Ltd 647