Plasma levels of TNF-α, IFN-γ, IL-4 and IL-10 during a course of experimental contagious bovine pleuropneumonia

Background: Contagious Bovine Pleuropneumonia (CBPP), caused by Mycoplasma mycoides subsp. mycoides, is widespread in sub-Saharan Africa. The current live vaccine T1/44 has limited efficacy and occasionally leads to severe side effects in the animals. A better understanding of the immune responses triggered by Mycoplasma mycoides subsp. mycoides and their role in disease progression will help to facilitate the design of a rational vaccine. Currently, knowledge of cytokines involved in immunity and immunopathology in CBPP is rather limited. The aim of this study was to characterize the in vivo plasma concentrations of the cytokines TNF-alpha, IFN-gamma, IL-4, IL-10 and the overall role of CD4(+) T cells in the development of cytokine levels during a primary infection. Plasma cytokine concentrations in two groups of cattle (CD4(+) T cell-depleted and non-depleted cattle) experimentally infected with Mycoplasma mycoides subsp. mycoides were measured and their relationship to the clinical outcomes was investigated. Results: Plasma cytokine concentrations varied between animals in each group. Depletion of CD4(+) T cells did not induce significant changes in plasma levels of TNF-alpha, IL-4, and IL-10, suggesting a minor role of CD4(+) T cells in regulation or production of the three cytokines during the time window of depletion (1-2 weeks post depletion). Unexpectedly, the IFN-gamma concentrations were slightly, but statistically significantly higher in the depleted group (p < 0.05) between week three and four post infection. Three CD4(+) T cell-depleted animals that experienced severe disease, had high levels of TNF-alpha and IFN-gamma. Only one severely diseased non-depleted animal showed a high serum concentration of IL-4 post infection. Conclusions: Comparison of most severely diseased animals, which had to be euthanized prior to the expected date, versus less severe diseased animals, irrespective of the depletion status, suggested that high TNF-alpha levels are correlated with more severe pathology in concomitance with high IFN-gamma levels.