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ABSTRACTThe acute phase of Mediterranean spotted fever (MSF) is characterized by dramatic changes in cytokine production patterns, clearly indicating their role in the immunomodulation of the response against the microorganism, and the differences in cytokine production seem to influence the extent and severity of the disease. In this study, the single nucleotide polymorphisms (SNPs) of tumor necrosis factor alpha (TNF-a) -308G/A (rs1800629) and interleukin-10 (IL-10) -1087G/A (rs1800896), -824C/T (rs1800871), and -597C/A (rs1800872) and the gamma interferon (IFN-?) T/A SNP at position +874 (rs2430561) were typed in 80 Sicilian patients affected by MSF and in 288 control subjects matched for age, gender, and geographic origin. No significant differences in TNF-a -308G/A genotype frequencies were observed. The +874TT genotype, associated with an increased production of IFN-?, was found to be significantly less frequent in MSF patients than in the control group (odds ratio [OR], 0.18; 95% confidence interval [95% CI], 0.06 to 0.51; Pcorrected for the number of genotypes [Pc], 0.0021). In addition, when evaluating the IFN-? and IL-10 genotype interaction, a significant increase of +874AA/-597CA (OR, 5.31; 95% CI, 2.37 to 11.88; Pc, 0.0027) combined genotypes was observed. In conclusion, our data strongly suggest that finely genetically tuned cytokine production may play a crucial role in the regulation of the immune response against rickettsial infection, therefore influencing the disease outcomes, ranging from nonapparent or subclinical condition to overt or fatal disease.

ABSTRACTA retrospective analysis by molecular-sequence-based techniques was performed to correctly identify the etiological agent of 24 Mediterranean spotted fever cases occurring in Western Sicily, Italy, from 1987 to 2001. Restriction analysis of a 632-bp PCR-amplified portion of the ompAgene allowed presumptive identification of five clinical isolates as belonging to Rickettsia conoriisubsp. israelensis, the etiological agent of Israeli spotted fever (ISF). The remaining 19 rickettsial isolates were Rickettsia conoriisubsp. conorii, the only pathogenic rickettsia of the spotted fever group reported in Italy until the present. Sequence analysis of the ompAgene confirmed the identification of all the R. conoriisubsp. israelensisisolates and demonstrated that rickettsiosis caused by R. conoriisubsp. israelensiscan be traced back to 1991 in Sicily. The recorded clinical data of the five ISF patients support the idea that these strains could correlate to more-severe forms of human disease. Three of five patients experienced severe disease, and one of them died.

Sera from Sicilian patients with confirmed visceral leishmaniasis (Leishmania donovani infantum) were analysed at the moment of the diagnosis, during the course of the disease and after clinical recovery, for the concentration of IL-10, IFN- γ, IL-4 and IL-2. The results show high concentrations of IL-10 and IFN- γ in the sera at the beginning of infection that return to the normal range following successful chemotherapy. By contrast, PBMC stimulated in vitro with Ag and mitogen produced low levels of IL-10 and IFN- γ when collected at the time of the diagnosis and normal levels when assayed after recovery. IL-2 was undetected in the sera and was significantly reduced in the supernatants of actively infected patients, returning to the normal level after recovery. IL-4 was absent in the sera and in high concentrations in the supernatants in all the phases of the disease. The levels of CD4+and CD8+T cells were within the normal range, but acute VL patients had markedly reduced levels of memory T cells (CD3+/CD45RO+) compared with healthy controls. These cells returned to the normal levels following successful chemotherapy. T cells are strongly activated in acute VL patients as indicated by the elevated number of CD3+HLA-DR+and by the increase in HLA-DR antigen on these cells. There was a significant reduction in the cell membrane DR antigen of the monocytes (CD 14+) during the acute phase of the disease, but it returned to the normal range after clinical recovery. These findings therefore suggest that in Sicilian patients with active VL the cytokine profile is not clearly characterized by Th2 phenotype as in mice, and both Th1-like and Th2-like cells appear to proliferate and to be activated. Furthermore, IL-10, rather than IL-4, could play an important part in the inhibition of IFN- γ-induced macrophage activation and could reflect the levels of HLA-DR antigen expressed by the monocytes.

We describe a case of the isolation of Bartonella quintanafrom the parotid gland of an apparently healthy man. Pathological examination showed intraparotid granulomatous abscessual lymphadenitis. Diagnosis was made on the basis of high titers of immunoglobulin G (IgG) and IgM antibodies and of culture isolation of a causative agent from parotid aspirate.

Interferon (IFN)-γ, interleukin (IL)-10, IL-6, and tumor necrosis factor (TNF)-α were significantlyincreased in sera from Sicilian patients with acute boutonneuse fever (BF) compared with those ofhealthy controls. IFN-γ levels dropped sharply within the second week after infection. IL-6, IL-10,and TNF-α levels gradually declined; in convalescent patients only were they in the normal range.In contrast, peripheral blood mononuclear cells (PBMC) stimulated in vitro with phytohemagglutinin(PHA) produced low levelsof IL-10 and IFN-γ in acute BF that were compatible with the reductionin the levels of CD4+, CD4+/CD45RO+, and CD4+ICD45RA+ cells. In vitro production of TNF-α and IL-6 from PBMC stimulated with PHA was not significantly modified during the various phases of the infection compared with control PBMC, which could be due to the persistence of high levels of CD14+ monocytes compensating for the decrease in CD20+ B cells.

Sera and urine samples from 115 Sicilian patients with boutonneuse fever (BF), obtained at thetime of diagnosis and after clinical recovery, were analyzed for concentrations of interleukin (IL)-2 and soluble IL-2 receptor (sIL-2R). There were significantly high levels of sIL-2R in the urine and sera of patients with acute BF compared with healthy controls, and the values returned to normal following successful chemotherapy. The data indicate that the sIL-2R urine concentrations correlated directly with the sIL-2R sera levels. In contrast, in all tested sera and urine samples, IL-2 levels were normal. Furthermore, a reduction in IL-2 production by peripheral blood mononuclear cells from acute BF patients was also observed. sIL-2R represents an unspecific marker useful to monitor the evolution of BF.