Differential production of interleukin-1 family cytokines (IL-1 beta, IL-18, IL-33 and IL-37) in patients with paracoccidioidomycosis: correlation with clinical form and antifungal therapy

Author(s)

Rocha Moreira Alves, Andre Bueno ^[1] ; David, Murilo Amato ^[1] ; de Castro, Livia Furquim ^[2] ; da Silva, Rosiane Maria ^[2] ; Longhi, Larissa Nara Alegrini ^[2] ; de Souza Lima Blotta, Maria Heloisa ^[2] ; Mamoni, Ronei Luciano ^{[2, 1]}

Affiliation

^[1] FMJ, Dept Morphol & Basic Pathol, Jundiai, SP - Brazil

^[2] Univ Campinas UNICAMP, Fac Med Sci, Dept Clin Pathol, BR-13083970 Campinas, SP - Brazil

• Document type: Journal article
• Source: Medical Mycology; v. 56, n. 3, p. 332-343, APR 2018.
• Web of Science Citations: 3

Abstract

Besides interleukin (IL)-1 beta and IL-18, the newly described cytokines of family IL-33 and IL-37 can contribute to the differentiation and maintenance of different population of T cells. IL-33 acts as an allarmin and promotes a predominant Th2 inflammatory response, whereas IL-37 plays an important role as an antagonist of inflammation. In paracoccidioidomycosis (PCM), caused by the dimorphic fungi Paracoccidioides brasiliensis and P. utzii, it has been shown that the acquired immune responses are associated with the diverse clinical manifestations. The severe and disseminated forms (acute form {[}AF] and multifocal chronic form {[}CF-MF]) are characterized by high Th2 cytokines and antibody production, impaired cellular immune response, and eosinophilia. In contrast, in the localized form (unifocal chronic form {[}CF-UF]), the cellular immune response is preserved, with high production of Th1 and Th17 cytokines, and low antibody titers. This study aimed to quantify interleukin-1 family cytokines (IL-1 beta, IL-18, IL-37, IL-33, and the soluble IL-33 receptor sST2) in sera of patients presenting different clinical forms of PCM before, during, and after antifungal treatment, as well as to analyze the expression of these cytokines in lesions of PCM patients. We found that AF patients presented high serum levels of IL-1 beta, IL-18, IL-33, sST2, and IL-37, and that these cytokines are strongly expressed in lymph nodes lesions. Furthermore, antifungal therapy resulted in the diminution of circulating cytokines and sST2 levels in all groups of patients. These results indicate that, besides IL-1 beta and IL-18, IL-33, IL-37, and sST2 can be associated with the disease activity and severity. (AU)

• FAPESP's process: 13/24286-0 - Participation of the inflammasome NLRP3 and cytokines from the IL-1 family in the infammatory response induced by the pathogenic fungi Paracoccidioides brasiliensis and Candida albicans
• Grantee: Ronei Luciano Mamoni
• Support Opportunities: Regular Research Grants