title: Treatment of experimental disseminated Mycobacterium avium complex infection in mice with recombinant IL-2 and tumor necrosis factor.
abstract: Mycobacterium avium complex (MAC) is the most common bloodstream pathogen isolated from patients with AIDS. We have previously shown that TNF alone or in combination with IL-2 can activate human and murine macrophages in vitro to kill MAC strains isolated from disseminated infections. To determine whether treatment with TNF and IL-2 could effect the course of disseminated MAC infections in a murine model of disseminated MAC infection, we infected C57BL mice with 3 x 10(8) bacteria i.v. and 1 wk later administered: 1) IL-2, 100 micrograms/kg; 2) TNF, 25 micrograms/kg; 3) IL-2, 50 micrograms/kg, and TNF, 12.5 micrograms/kg; and 4) saline. IL-2 was injected i.p. daily with TNF being administered in cycles of 3 out of 4 consecutive days. Fourteen days after starting therapy, blood was cultured and mice were sacrificed for quantitative cultures of liver and spleen homogenates. IL-2, TNF, and IL-2/TNF treated groups showed an 87 +/- 5%, 57 +/- 9%, 88 +/- 6% decrease in bacteremia (p = 0.05 for TNF-treated animals and less than 0.04 for the other two groups, compared with control). The combination IL-2/TNF was the only treatment that showed a trend toward an absolute decrease in the number of bacteria in the blood. Reduction in colony counts of liver and spleen were 77 +/- 4% and 87 +/- 6%, respectively, for treatment with IL-2, 58 +/- 7% and 87 +/- 5% for TNF, and 60 +/- 10% and 82 +/- 6% for IL-2/TNF, respectively. These results suggest that both cytokines may play a role in the control of Mycobacterium avium infection and that the combination of a half-dose of IL-2 and TNF, despite not showing any greater efficacy, can be less toxic than TNF or IL-2 alone and might be useful for the therapy of disseminated infection.
authors.affiliation: Kuzell Institute for Arthritis and Infectious Diseases, Medical Research Institute of San Francisco, Pacific Presbyterian Medical Center, CA 94115.
authors.forename: L E
authors.initials: LE
authors.lastname: Bermudez
authors.forename: P
authors.initials: P
authors.lastname: Stevens
authors.forename: P
authors.initials: P
authors.lastname: Kolonoski
authors.forename: M
authors.initials: M
authors.lastname: Wu
authors.forename: L S
authors.initials: LS
authors.lastname: Young
mesh_terms: D000818:Animals; D001770:Blood Bactericidal Activity; D007167:Immunotherapy; D007376:Interleukin-2 / Q000627:therapeutic use*; D008099:Liver / Q000382:microbiology; D008262:Macrophage Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D015270:Mycobacterium avium-intracellulare Infection / Q000628:therapy*; D011994:Recombinant Proteins; D013154:Spleen / Q000382:microbiology; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*
chemical_list: D007376:Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides