SUMMARYSera from nine Sicilian patients with ennlirmed visceral leishmaniasis {Leishmania donovani infantuni; VL). at the moment of the diagnosis, during the eourse of the disease and after clinical recovery, were analysed for the concentration of soluble IL-2 receptor (slL-2R). The results show that slL-2R is a marker of disease activity, since it is in high concentration at the beginning of infeetion and returns to the normal range following successful chemotherapy. At the same time of serum analysis for slL-2R, peripheral blood mononuclcar cells (PBMC) of VL patients were stimulated with phytohaemagglutinin (PHA) or antigen and supernatant tested for lL-2 and interferon-gamma (IFN-y) production. Data demonstrate that there is an inverse relation between concentration of IL-2 and !FN--/ in the supernatants and sIL-2R secretion in the sera.
Ex vivo culture of spleen cells from BALB/c mice infected with 2 x 10(6) Leishmania major (L. major) promastigotes were cultured with ConcanavalinA (ConA) or leishmanial antigen (L. Ag) and tested for prostaglandin E2 (PGE2) and for leukotriene B4 (LTB4), in order to study their involvement in the evolution of cutaneous leishmaniasis and the connexion with lymphokine-mediated responses. The data were compared with those obtained in BALB/c mice protected against L. major by sublethal irradiation (550 rad; cured mice). In the unprotected BALB/c mice the levels of PGE2 that were responsible for the depression of interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF alpha) Th1-associated cytokines and for the relative increase in the interleukin-4 (IL-4) became higher and higher as the lesion progressed. On the contrary, the cured mice produced levels of PGE2 similar to normal uninfected controls, high levels of TNF alpha and IFN-gamma and low levels of IL-4. Elevated levels of LTB4 were detected in the early stage of infection in the unprotected mice compared to cured ones, a sign of more intense inflammation and a stimulus for the recruitment of inflammatory cells. The observation that exogenous LTB4 was able to enhance in vitro both Th1 cytokines in cured mice and Th2 cytokines in unprotected ones suggests that LTB4 could act in the recruitment of the T cells already committed to Th1 or Th2 phenotype.
Our model was thus able to identify patients at higher risk of death. These results confirm the importance of cancer geriatric assessment also for the clinical evaluation of oncological patients. Additional randomized studies with a larger number of patients, also in an adjuvant setting, should be performed to confirm the effectiveness of this approach.
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