PMID- 14670321 OWN - NLM STAT- MEDLINE DCOM- 20040319 LR - 20190728 IS - 0264-410X (Print) IS - 0264-410X (Linking) VI - 22 IP - 3-4 DP - 2004 Jan 2 TI - Induction of persistent in vivo resistance to Mycobacterium avium infection in BALB/c mice injected with interleukin-18-secreting fibroblasts. PG - 398-406 AB - Interferon-gamma (IFN-gamma) is closely associated with the generation of cell-mediated immunity and resistance to intracellular parasites. Interleukin-18 (IL-18) is known to strongly induce IFN-gamma production by T cells and natural killer (NK) cells. To determine whether the paracrine secretion of IL-18 can efficiently stimulate the resistance to Mycobacterium avium complex (MAC) infection, 3T3 fibroblasts were stably transfected to secrete bioactive IL-18 and their effects on MAC infection were investigated in genetically susceptible BALB/c mice, compared with that of free recombinant IL-18. Immunization with IL-18-secreting fibroblasts (3T3/IL-18) during intranasal infection with MAC resulted in a significant decrease in bacterial load of lung during the entire 8-week observation period, while rIL-18 reduced the bacterial load at initial 1 week but not by 8 weeks postinfection. Immunization with the 3T3/IL-18 cells induced and maintained significantly higher levels of cytotoxic activity and nitric oxide production by lung cells than those of rIL-18 immunization. Furthermore, lung cells in mice injected with the 3T3/IL-18 cells showed persistent production of IFN-gamma throughout the 8-week period, suggesting that the 3T3/IL-18 cells induced the resistance to MAC infection via IFN-gamma production. This work suggests that IL-18-secreting fibroblasts may serve as a vehicle for paracrine secretion of IL-18 in immunotherapy of MAC infection. FAU - Chung, Su W AU - Chung SW AD - Department of Pharmacy, College of Pharmacy, Chonnam National University, 500-757 Kwangju, Republic of Korea. FAU - Choi, Sang H AU - Choi SH FAU - Kim, Tae S AU - Kim TS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (Antibodies, Monoclonal) RN - 0 (Cytokines) RN - 0 (Indicators and Reagents) RN - 0 (Interleukin-18) RN - 31C4KY9ESH (Nitric Oxide) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - 3T3 Cells MH - Animals MH - Antibodies, Monoclonal/biosynthesis/pharmacology MH - Blotting, Western MH - Cytokines/biosynthesis MH - Electrophoresis, Polyacrylamide Gel MH - Female MH - Fibroblasts/*metabolism MH - Genetic Vectors/genetics MH - Indicators and Reagents MH - Interferon-gamma/immunology MH - Interleukin-18/*metabolism MH - Lung/cytology MH - Mice MH - Mice, Inbred BALB C MH - Mycobacterium avium Complex/*immunology MH - Mycobacterium avium-intracellulare Infection/*immunology/microbiology/*prevention & control MH - Nitric Oxide/metabolism MH - Retroviridae/genetics MH - Reverse Transcriptase Polymerase Chain Reaction MH - T-Lymphocyte Subsets/immunology MH - Transfection EDAT- 2003/12/13 05:00 MHDA- 2004/03/20 05:00 CRDT- 2003/12/13 05:00 PHST- 2003/12/13 05:00 [pubmed] PHST- 2004/03/20 05:00 [medline] PHST- 2003/12/13 05:00 [entrez] AID - S0264410X0300584X [pii] AID - 10.1016/j.vaccine.2003.07.002 [doi] PST - ppublish SO - Vaccine. 2004 Jan 2;22(3-4):398-406. doi: 10.1016/j.vaccine.2003.07.002.