Interleukin-12-secreting fibroblasts are more efficient than free recombinant interleukin-12 in inducing the persistent resistance to Mycobacterium avium complex infection.
To determine whether the paracrine secretion of interleukin-12 (IL-12) can efficiently stimulate the resistance to Mycobacterium avium complex (MAC) infection, 3T3 fibroblasts were stably transfected to secrete IL-12 (480 U/106 cells/48 hr) and their effect on MAC infection was investigated in genetically susceptible BALB/c mice, compared with that of free recombinant IL-12 (rIL-12). Injection with IL-12-secreting fibroblasts (3T3-IL-12) during intranasal infection with MAC resulted in a significant decrease in the bacterial load of the lung during the entire 10-week observation period, while rIL-12 reduced the bacterial load initially, at 2 weeks, but not by 10 weeks postinfection. Lung CD4+ T cells in mice injected with the 3T3-IL-12 cells showed a persistent T helper type 1 (Th1) response throughout the 10-week period. Furthermore, immunization with the 3T3-IL-12 cells induced and maintained significantly higher levels of cytotoxic activity and nitric oxide production by lung cells than did rIL-12 immunization. This work suggests that IL-12-secreting fibroblasts may serve as a vehicle for paracrine secretion of IL-12 for immunotherapy of MAC infection.
Kang
B Y
BY
College of Pharmacy, Chonnam National University, Kwangju, Korea.
Chung
S W
SW
Lim
Y S
YS
Kim
E J
EJ
Kim
S H
SH
Hwang
S Y
SY
Kim
T S
TS
D000818:Animals; D003602:Cytotoxicity, Immunologic; D005260:Female; D005347:Fibroblasts / Q000276:immunology* / Q000637:transplantation; D007114:Immunization; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000276:immunology; D008168:Lung / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology
D011994:Recombinant Proteins; D018664:Interleukin-12; D009569:Nitric Oxide