PMID- 7523434 OWN - NLM STAT- MEDLINE DCOM- 19941024 LR - 20190920 IS - 0271-9142 (Print) IS - 0271-9142 (Linking) VI - 14 IP - 3 DP - 1994 May TI - Modulation of immunoglobulin production and cytokine mRNA expression in peripheral blood mononuclear cells by intravenous immunoglobulin. PG - 178-89 AB - Intravenous immunoglobulin (IVIG) has the potential to regulate Ig production, but the mechanism(s) responsible for this effect is unknown. In experiments reported here, we examined the ability of IVIG to regulate Ig production in human peripheral blood mononuclear cells (PBMCs) stimulated with pokeweed mitogen (PWM). IVIG (2-10 mg/ml) showed a potent (80-85%) inhibition of PWM-stimulated IgG, IgM, and IgA production. To determine more precisely how IVIG mediated the inhibition of Ig production, we studied Ig promoting cytokine gene expression after PWM stimulation with or without IVIG (2 and 10 mg/ml) using dot-blot techniques. RNA was isolated from PBMCs at predetermined time points and probed with cDNAs specific for human cytokines (IL-1 beta, IL-2, IL-2R, IL-4, IL-5, IL-6, gamma-IFN, and TNF-alpha). IL-6 mRNA accumulation was maximal at 4.5 hr post-PWM stimulation and was inhibited 64-75% when IVIG (10 mg/ml) was present. gamma-IFN mRNA levels peaked at 72 hr poststimulation and were also 68-75% inhibited by IVIG. IL-2 mRNA levels peaked at 4.5 hr and were 23-46% inhibited by IVIG. The inhibitory effect of IVIG on production of these cytokines (IL-6 and gamma-IFN) was also observed at the protein level in sonicated PBMCs after incubation with PWM and IVIG. The mRNA levels for other cytokines were not or only minimally inhibited by IVIG. Addition of IL-6, gamma-IFN, or IL-2 partially restored Ig production in IVIG-treated PWM-stimulated cultures, suggesting that inhibition of other cytokines or another mechanism(s) independent of cytokine inhibition might also be involved, although inhibition of IL-6, gamma-IFN, and IL-2 may be one of the critical factors in the suppression of Ig production by IVIG. FAU - Toyoda, M AU - Toyoda M AD - Ahmanson Pediatrics Center, Steven Spielberg Pediatric Research Laboratory, Cedars-Sinai Medical Center/University of California, Los Angeles School of Medicine 90048. FAU - Zhang, X AU - Zhang X FAU - Petrosian, A AU - Petrosian A FAU - Galera, O A AU - Galera OA FAU - Wang, S J AU - Wang SJ FAU - Jordan, S C AU - Jordan SC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - J Clin Immunol JT - Journal of clinical immunology JID - 8102137 RN - 0 (Cytokines) RN - 0 (DNA Probes) RN - 0 (Immunoglobulins) RN - 0 (Immunoglobulins, Intravenous) RN - 0 (Pokeweed Mitogens) RN - 0 (RNA, Messenger) RN - 63231-63-0 (RNA) SB - IM MH - Cells, Cultured MH - Cytokines/*genetics/*immunology MH - DNA Probes MH - Enzyme-Linked Immunosorbent Assay MH - Gene Expression MH - Humans MH - Immunoglobulins/*biosynthesis MH - Immunoglobulins, Intravenous/*immunology MH - Lymphocyte Activation MH - Lymphocytes/*immunology MH - Pokeweed Mitogens MH - RNA/isolation & purification MH - RNA, Messenger/*biosynthesis EDAT- 1994/05/01 00:00 MHDA- 1994/05/01 00:01 CRDT- 1994/05/01 00:00 PHST- 1994/05/01 00:00 [pubmed] PHST- 1994/05/01 00:01 [medline] PHST- 1994/05/01 00:00 [entrez] AID - 10.1007/BF01533367 [doi] PST - ppublish SO - J Clin Immunol. 1994 May;14(3):178-89. doi: 10.1007/BF01533367.