Effect of ovaric hyper-stimulation on blood lymphocyte subpopulations, cytokines, leptin and nitrite among patients with unexplained infertility.

PROBLEM: To determine the effect of ovarian stimulation on TH1, TH2 and natural killer (NK) lymphocytes, plasma cytokines, leptin and nitrite levels. METHODS: Women with reproductive failure were studied during the implantation window, at baseline (n = 18) and under ovarian stimulation (gonadotropins + progesterone, n = 6). CONTROLS: eight fertile women. Lymphocyte subpopulations and NK function were determined by flow cytometry. Interleukin-2 (IL-2), IL-4, IL-10, IFN-gamma, TNF-alpha, TGF-beta1 and leptin were measured by enzyme immunoassay (EIA); nitrite by the Griess reaction. RESULTS: At baseline, patients had higher values of NK effectors, NK activity and plasma IFN-gamma and IL-2 than controls. Conversely, TGF-beta1 values were lower. Hormones induced leukocytosis. Under stimulation, THI CD4+ cells, NK effectors and function and plasma IFN-gamma and IL-2 decreased, while transforming growth factor (TGF)-beta1 increased. Other variables did not change. CONCLUSION: The abnormal distribution of leukocytes, high TH1 cytokines and a low TGF-beta1 associated with reproductive failure, respond to ovarian stimulation, achieving total or partial normalization.

High serum interleukin-10 and tumor necrosis factor alpha levels in chronic paracoccidioidomycosis.

In patients with chronic paracoccidioidomycosis (n = 10), levels of tumor necrosis factor alpha, interleukin-10, and interleukin-2 in serum, measured by enzyme-linked immunosorbent assay (in picograms per milliliter, as mean +/- standard error of the mean), were higher than in normal controls (n = 8): 186 +/- 40 versus 40 +/- 7 (P < 0.05), 203 +/- 95 versus 20 +/- 8 (P = 0.001), and 96.3 +/- 78.57 versus 1.19 +/- 1.19 (P = 0.045), respectively. Gamma interferon and interleukin-4 levels were similar in patients and controls.

Neutrophil respiratory burst activity and pro- and anti-inflammatory cytokines in AAA surgery: conventional versus endoluminal treatment.

PURPOSE: To examine the inflammatory impact of endovascular and conventional surgery of abdominal aortic aneurysm (AAA) as assessed by the activation of neutrophils and serum levels of pro- and anti-inflammatory cytokines. METHODS: Twenty-four patients undergoing AAA exclusion were treated with either endovascular (n = 14) or conventional (n=10) techniques. Clinical and hematological data, respiratory burst of neutrophils, and the expression of adhesion and activation molecules (CD18, CD11b, CD69, and HLA-DR) were analyzed by flow cytometry. The enzyme-linked immunosorbent assay technique was used to measure proinflammatory cytokine interleukin (IL)-8 and anti-inflammatory cytokines IL-1 receptor antagonist (IL-1RA) and transforming growth factor beta1 (TGF-beta1). RESULTS: All patients, most of whom had normal cytokine values before surgery, were successfully treated. No significant changes were found in surface antigens. Basal respiratory burst was quite heterogeneous; in all cases respiratory burst activity decreased after surgery and remained low throughout the observation period. Despite marked interpatient differences, IL-1RA and IL-8 increased after surgery, whereas TGF-beta1 decreased, although the variation achieved statistical significance only in the conventional group. Elevated IL-1RA returned to normal within 48 hours in the endoluminal group, whereas the level remained high in the conventional group in the last sample. CONCLUSIONS: Despite heterogeneity before surgery, the respiratory burst decreased for most of the patients regardless of the approach, and both techniques increased IL-1RA. Although both procedures seemed to decrease TGF-beta1, the difference was significant only with the conventional approach. IL-1RA levels fell toward basal values quicker in the endograft patients, suggesting that the endoluminal approach was less aggressive.

In vivo effect of snake phospholipase A2 (crotoxin+cardiotoxin) on serum IL-1alpha, TNF-alpha and IL-1ra level in humans.

VRCTC-310-Onco (crotoxin, a secretory phospholipase A2+cardiotoxin) is under development as an anti-neoplastic agent. Pro-inflammatory cytokines TNF-alpha and interleukin 1 alpha (IL-1alpha) and anti-inflammatory cytokine IL-1 receptor antagonist (IL-1ra) were measured with commercial ELISA kits in sera corresponding to 23 cycles with doses between 0.0025 and 0.023 microg/kg body weight, obtained during the phase I trial of VRCTC-310-Onco. Neither serum TNF-alpha nor IL-1alpha did change significantly after VRCTC-310-Onco. Basal IL-1ra was 794 +/- 97 pg/ml, by 3 h it was similar, 651 +/- 99 pg/ml and at 24 h p.i. it increased to 1197 +/- 122 pg/ml (P<0.001). The increase was dose-dependent. The addition of dexamethasone (required to reduce pain with the highest doses) inhibited IL-1alpha and enhanced the induction of IL-1ra by VRCTC-310-Onco. Summing up, in vivo, in humans, in the dose range tested, VRCTC-310-Onco induces IL-1ra, and does not consistently modify IL-1alpha or TNF-alpha serum levels.