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Published on: April 8, 2016
Differential correlation between interleukin patterns in disseminated and chronic human paracoccidioidomycosis
C L Silva1, M F Silva, L H Faccioli
1Department of Parasitology, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
Insights
This study reveals that inflammatory cytokines like IL-1, IL-6, and TNF are elevated in disseminated paracoccidioidomycosis (PCM), correlating with high antibody levels and suppressed immune responses. These findings highlight the role of cytokines in PCM pathogenesis and immune dysregulation.
Area of Science:
- Immunology
- Infectious Diseases
- Clinical Medicine
Background:
- Paracoccidioidomycosis (PCM) is an infectious disease with complex immunoregulatory disorders.
- Understanding the interplay of cytokines, antibody levels, and immune cell responses is crucial for managing PCM.
Purpose of the Study:
- To investigate the correlation between interleukin patterns, lymphoproliferation, C-reactive protein (CRP), and specific antibody levels in different clinical forms of PCM.
- To elucidate the role of inflammatory cytokines in the pathogenesis and immune dysregulation observed in PCM.
Main Methods:
- Studied 16 PCM patients across disseminated (treated and non-treated) and chronic forms.
- Measured serum levels of tumor necrosis factor (TNF), IL-1, IL-6, IL-4, IL-2, and C-reactive protein (CRP).
- Assessed specific antibody titers against Paracoccidioides brasiliensis and peripheral blood mononuclear cell (PBMC) response to phytohaemagglutinin (PHA).
Main Results:
- Non-treated disseminated PCM patients showed increased TNF, IL-1, IL-6, and CRP, correlating with high antibody titers and low PBMC response to PHA.
- Positive correlations were observed between IL-1, IL-6, TNF, and CRP in disseminated PCM.
- Inverse correlations were found between IL-4 and antibody production in non-treated disseminated PCM, and between IL-2 and antibody production in chronic PCM.
Conclusions:
- Inflammatory cytokines play a pivotal role in the development and control of paracoccidioidomycosis.
- Cytokine profiles are associated with specific clinical forms and immune dysregulation, including hypergammaglobulinaemia and depressed T cell-mediated immunity.
- Findings suggest potential therapeutic targets related to cytokine modulation in PCM management.
Abstract:
In an attempt to understand better the immunoregulatory disorders in paracoccidioidomycosis (PCM), the possible correlation between interleukin pattern, lymphoproliferation, C-reactive protein (CRP) and specific antibody levels was investigated in the polarized clinical forms of this disease. We studied 16 PCM patients, eight with the disseminated disease (four under treatment and four non-treated) and eight with the chronic disease. The patients with disseminated disease exhibited high antibody titres specific to Paracoccidioides brasiliensis antigen compared with patients with the chronic form of disease. Tumour necrosis factor (TNF), IL-1, IL-6 and CRP in the serum of non-treated disseminated PCM patients were increased, which correlated positively with the low mitogenic response of peripheral blood mononuclear cells (PBMC) to phytohaemagglutinin (PHA) (P < 0.01) and with the high antibody titres (P < 0.001) of these patients. Moreover, we found in the disseminated PCM patients positive correlations between IL-1 and IL-6 (P = 0.0007); IL-1 and TNF (P = 0.0045); IL-1 and IL-6 with the high antibody titres (P = 0.0834 and P = 0.0631, respectively); IL-1, IL-6 and TNF with CRP levels. By contrast, no correlations were found with those interleukins in the treated disseminated and chronic patients or in controls. It was interesting to find an inverse correlation between IL-4 and antibody production in non-treated disseminated PCM (r = -0.4770); moreover, a significant correlation (P = 0.0820) was found in chronic PCM patients with respect to the low level of either IL-4 and antibody titres against fungus antigen. Chronic PCM patients also had IL-2 levels inversely correlated with antibody production (r = -0.6313; P = 0.0628). Inverse correlations were also observed between IL-2 and IL-6 levels in non-treated disseminated patients (P = 0.0501) and between IL-2 and IL-4 in chronic patients (P = 0.0131). The inflammatory cytokines might have a pivotal role in the genesis and in control of some aspects of the disease, such as granulomatous reaction, hypergammaglobulinaemia and depression of T cell-mediated immunity in PCM.
