From December 1991 through January 1995, a disease survey was conducted on herds of free-ranging, hunter-killed elk (Cervus elaphus nelsoni) from three areas in proximity to Yellowstone National Park ...(YNP), Wyoming (USA), after tuberculosis caused by Mycobacterium bovis was discovered in a captive herd of elk in the area. Complete or partial sets of specimens from 289 elk collected between December 1991 and January 1993 were examined histologically: no mycobacterial lesions were observed. Lesions of tuberculosis were not detected in tonsils or lymph nodes of the head from an additional 99 hunter-killed, adult elk from one area (area 2) collected in January 1995. Neither M. bovis nor M. paratuberctdosis were isolated from any of the specimens cultured. Antibodies to Brucella abortus were detected in serum samples from 0%, 1%, and 1% of elk from three areas sampled (areas 1, 2, and 3), respectively. Brucella abortus biovar 1 was isolated from multiple tissues from one seropositive animal from area 3. Larvae with morphology consistent with Dictyocaulus sp. were found in 12%, 14%, and 0% of fecal specimens tested from areas 1, 2, and 3, respectively. Pasteurella multocida and Actinomyces pyogenes were isolated from a lung with purulent bronchopneumonia and abscesses.
The ex vivo effects of macrophage colony-stimulating factor (M-CSF) on antifungal and antibacterial activities of human elutriated monocytes were studied. Cells were isolated prior to the initiation ...of therapy, on day 3 and at week 7, in six patients with an advanced malignancy receiving M-CSF in a phase I study. Superoxide anion production by monocytes in response to N-formyl methionyl leucyl phenylalanine was enhanced at day 3 of therapy (
P=0.011). In addition, at day 3, fungicidal activity against blastoconidia of
Candida albicanswas enhanced by M-CSF treatment (
P=0.026), whereas antifungal activity against hyphae of
Aspergillus fumigatuswas not significantly changed. Bactericidal activity against
Staphylococcus aureuswas increased at day 3 (
P=0.004). By Northern blot analysis, M-CSF does not upregulate the expression of components of the NADPH-oxidase, the multi- component enzyme system responsible for generation of superoxide radicals by monocytes. Instead, the predominant effect of M-CSF on circulating monocytes is probably a post-transcriptional effect. In conclusion, these findings suggest that administration of M-CSF to patients may enhance microbicidal activities and thus may provide a useful adjunct to conventional antimicrobial therapy.
We performed functional assays on polymorphonuclear (PMN) leukocytes from 21 patients with advanced cancers, before, during, and after IL-2 administration. Of these, 19 were treated with high dose ...bolus IL-2 infusions (10(5) U/kg every 8 h) and 2 patients received low dose continuous infusions of IL-2 (250 U/kg/h). Five of six patients studied after IL-2 therapy had a decrease in their PMN chemotactic response to FMLP after bolus IL-2 (mean 8 doses) or, after the 4th day of continuous infusion IL-2 (pre-IL-2 values of 82% +/- 17% to 45% +/- 1% post-IL-2, p2 less than 0.004) compared with normal control values. In 8 of 10 patients studied, PMN capacity to oxidize intracellular dichlorofluorescein dye, an indirect measurement of O2- production in response to PMA stimulation, decreased after IL-2 administration (pre-IL-2 mean dichlorofluorescein oxidation (by channel number) 243 +/- 128 vs 3-day post-IL-2 87 +/- 86, p2 less than 0.02). Furthermore, a marked decrease in Fc gamma R III (Leu-11, CD16) expression was observed in 12/13 patients' PMN studied after IL-2 therapy (mean percent of PMN population with positive FcR expression was 81.1 +/- 15.4% pre-IL-2 which decreased to 56.0 +/- 30.5% post-IL-2, p2 less than 0.001). Other PMN surface markers (My4, My7, ICAM-1, LFA1, LFA3, Mac1) did not change significantly. PMN-mediated antibody-dependent cellular cytotoxicity did not change after IL-2 therapy (only 4/15 patients demonstrated more than 50% reduction in antibody-dependent cellular cytotoxicity). PMN phagocytosis of Staphylococcus aureus was also not significantly altered by IL-2 administration in six patients studied (pre-IL-2, 99 +/- 17% vs 111 +/- 28% post-IL-2, p2 greater than 0.2). We conclude that the systemic administration of IL-2 by intermittent or continuous administration is associated with marked changes in PMN function and cell surface receptor expression. These alterations may contribute to the apparent increased susceptibility to bacterial infection observed in these patients.
