Dynamics in serum cytokine responses during acute and convalescent stages of Mediterranean spotted fever

Abstract

Mediterranean spotted fever (MSF) is a re-emerging rickettsiosis in Bulgaria after 20 years of absence (1972-1992), and it has since been affecting many people annually in the endemic regions of the country. The role of cytokines in MSF is still in the focus of research due to their complex participation in the immune pathogenesis of the disease. Aim: To study the changes in the serum cytokine concentrations in MSF patients. Patiends and Methods: Eighty patients with MSF and 20 healthy controls were enrolled in the study. The pro-inflammatory and immunoregulatory cytokines IL-1β, TNF-α, IL-6, IL-8, IL-12, IFN-γ, IL-2, and IL-10 were studied in the burst of disease, at clinical recovery stage, and two weeks later. The disease etiology was verified by indirect IFA in the Referral Rickettsiosis Laboratory. The cytokine levels were determined by EL ISA (BioSource Europe S.A). Results: In the disease flare up patients showed a manifold increase in the activity of IL- 1β (р < 0.01), TNF-α (p < 0.001), IL-6 (р < 0.001), and IL-8 (p < 0.001) compared with the controls. Significant elevation in IFN-γ and IL-12 values (p < 0.001) was also found. The increase in the immunoregulatory IL-10 also reached statistical significance (p < 0.001), while the rise in IL-2 did not (р > 0.05). Followed in dynamics, only IL-1β and IL-6 measured up the control levels at the time of clinical recovery. Two weeks later, in the early convalescence IL-12 and TNF-α further diminished but did not normalize their values. Conclusion: Our findings show that MSF is characterized by a Th1 cytokine profile. The patient’s immune system responds by proinflammatory and immunoregulatory cytokine production that accompanies the rickettsial vasculitis and contributes to the healing process. The latter is probably not fully achieved in the early convalescent period, according to our data concerning some pro-inflammatory cytokines’ elevation at this period.

Significantly Higher Cytokine and Chemokine Levels in Patients with Japanese Spotted Fever than in Those with Tsutsugamushi Disease

“…We previously reported that a downregulation of these cytokines and chemokines is observed after the administration of tetracyclines, demonstrated a correlation between the severity of TD and the serum concentration of TNF-␣ in the acute phase of the disease, and showed that TNF-␣ levels are predictive of the severity of TD (18,19,29,30). In relation to other spotted fever group infections, it is reported that Mediterranean spotted fever is characterized by a Th1 cytokine profile, and the patient's immune system responds with proinflammatory and immunoregulatory cytokine production (IL-1␤, TNF-␣, IL-6, IFN-␥, IL-8, IL-10, and IL-12) that accompanies the rickettsial vasculitis and contributes to the healing process (31). The cytokine profiles for JSF and MSF were not much different from each other.…”

Mediterranean Spotted Fever - Classification by Disease Course and Criteria for Determining the Disease Severity

“…IL-10 stimulates regulatory T lymphocytes (Treg) and inhibits the Th1 cell-mediated immune responses and as a consequence uncontrolled bacterial growth leads to 59 more serious outcomes of the disease. [26][27][28][29] Wrongly regulated activation and proliferation of lymphocytes may lead to severe and unusual complications. Genetic polymorphism of some cytokines (IFN-γ, TNF-α and IL-10) probably also plays a role in susceptibility to MSF.…”

Association of the TNF-α-308, TNF-α-238 gene polymorphisms with risk of bone-joint and spinal tuberculosis: a meta-analysis

“…TNF-α is a potent pleiotropic proinflammatory and immunoregulatory cytokine, which contributes to the initiation, up-regulation, and perpetuation of the inflammatory response. TNF-α is produced by many cell types including neutrophils, fibroblasts, NK cells, T and B cells, and macrophages infiltrating tissue as the part of host defense against brucellosis infection [5,6]. Increased levels of serum TNF-α has been observed in several infectious diseases including brucellosis [7,8], advanced tuberculosis [5], acute-phase Mediterranean spotted fever [6] and malaria.…”

“…TNF-α is produced by many cell types including neutrophils, fibroblasts, NK cells, T and B cells, and macrophages infiltrating tissue as the part of host defense against brucellosis infection [5,6]. Increased levels of serum TNF-α has been observed in several infectious diseases including brucellosis [7,8], advanced tuberculosis [5], acute-phase Mediterranean spotted fever [6] and malaria. In conclusion, TNF-α may be an important factor in the early anti-inflammatory effects of infection, and it may have the necessary protective effect in the chronic phase of infection.…”