title: 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.
  
  
  OBJECTIVE
  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-1beta, TNF-a, IL-6, IL-8, IL-12, IFN-gamma, 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 ELISA (BioSource Europe S.A).
  
  
  RESULTS
  In the disease flare up patients showed a manifold increase in the activity of IL-1beta (p < 0.01), TNF-alpha (p < 0.001), IL-6 (p < 0.001), and IL-8 (p < 0.001) compared with the controls. Significant elevation in IFN-gamma 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 (p > 0.05). Followed in dynamics, only IL-1beta 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-alpha further diminished but did not normalize their values.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Infectious Diseases, Parasitology and Tropical Medicine, Medical University, Plovdiv, Bulgaria. nelipop@yahoo.co.uk
authors.forename: Nedialka I
authors.initials: NI
authors.lastname: Popivanova
authors.forename: Mariana A
authors.initials: MA
authors.lastname: Murdjeva
authors.forename: Ivan G
authors.initials: IG
authors.lastname: Baltadzhiev
authors.forename: Irina A
authors.initials: IA
authors.lastname: Haydushka
mesh_terms: D000208:Acute Disease; D015415:Biomarkers / Q000097:blood; D001907:Boutonneuse Fever / Q000097:blood* / Q000453:epidemiology / Q000276:immunology; D002031:Bulgaria / Q000453:epidemiology; D003289:Convalescence; D016207:Cytokines / Q000097:blood*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009017:Morbidity / Q000639:trends
chemical_list: D015415:Biomarkers; D016207:Cytokines