Introduction: Infections by filamentous fungi, particularly Aspergillus spp., are increasing in incidence in immunocompromised patients and are associated with high morbidity and mortality. IL-15 is a Thl cytokine associated with the innate immune response, which has various enhancing effects on phagocytic function. IL-8 is a potent chemokine and TNF-alpha has broad proinflammatory properties. We hypothesised that IL-15 plays a role in modulation of the release of these two cytokines in response to Aspergillus spp. Methods: Polymorphonuclear leukocytes (PMNLs) were isolated by dextran sedimentation/ficoll centrifugation from blood obtained from healthy adult donors. Following pre-treatment of PMNLs with or without 100 rig/ml IL-15 for 22 hours, untreated and IL-15 treated PMNLs (1.5~ 10s/well) were incubated for 4 hours in HBSS, either unchallenged or challenged with hyphae of Aspergillus fumigatus, Aspergillus flavus or Verticillium nigrescens, a fungus of low pathogenicity, at E:T ratio 1O:l. The concentrations of IL-8 and TNF-alpha were then evaluated using ELISA. Results: A significant increase in IL-8 release by PMNLs was found in response to pre-treatment with IL-15 (n=5, by Student paired t test, all comparisons P-cO.05) when unchallenged (from 460a105 to 964~229 pg/ml) and when challenged with either A. fumigatus (from 1474_+334 to 3483_t777 pglml), or A. Jzavus (from 14122366 to 2653k501 pg/ml) or I/: nigrescens (from 1380+695 to 2190+760 pg/ml). In contrast, IL-15 did not have a significant effect on TNF-alpha release; however, very low levels of release were evident when challenged with the two Aspergillus spp. Conclusions: No significant increase in TNF-alpha release by human PMNLs occurs after IL-15 treatment. In contrast, IL-15 significantly enhances release of K-8, thus providing a mechanism for further recruitment of PMNLs in response to Aspergillus spp. and other filamentous fungi.
Full conference title:
12th International Symposium on Infections in the Immunocompromised Host
- ISIIH 12th