Immunomodulation of experimental pulmonary fibrosis by intravenous immunoglobulin (IVIG).
OBJECTIVE
To assess the immunomodulatory effect of intravenous immunoglobulin (IVIG) using an experimental model of bleomycin-induced pulmonary fibrosis.


METHODS
Pulmonary fibrosis was induced in C57BL/6 mice by direct intratracheal injection of bleomycin. Mice were treated with IVIG 1 week prior to (prevention protocol), or 10 days following bleomycin injection, when the disease was in progress. The controls used in the study included mice given phosphate buffered saline (PBS) and mice subjected to a commercial individual-IgG. Collagen-I deposits in the affected lungs were detected by Sirius red staining of paraffin embedded lung sections. The collagen-I content was measured by employing the hydroxyproline assay.


RESULTS
Prevention of bleomycin-induced pulmonary fibrosis by IVIG has been demonstrated by reduced expression of collagen-I protein in the affected lungs. The hydroxyproline levels in the lungs of the IVIG-treated mice were 214.33 +/- 13.56 microg/1 g tissue, compared to the higher levels in lungs of IgG treated mice (342.44 +/- 35.60 microg/1 g tissue) or untreated controls 328.00 +/- 45.55 microg/1 g tissue, (p < 0.0001). Effective treatment of bleomycin-induced pulmonary fibrosis by IVIG has been demonstrated by the reduced expression of collagen-I protein in the affected lungs, detected by sirius red histological staining. The hydroxyproline levels in the lungs of the IVIG-treated mice were 261.00 +/- 18.81 microg/1 g tissue, in comparison to the higher levels in the lungs of the IgG treated mice (342.43 +/- 32.89 microg/1 g tissue) and of untreated controls (344.33 +/- 49.85 microg/1 g tissue), (p < 0.001).


CONCLUSIONS
Based on these preliminary studies, we conclude that IVIG may have a beneficial effect in the down regulation of collagen-I levels in the lungs of mice with bleomycin-induced pulmonary fibrosis.
Molina
Vered
V
Department of Medicine B, The Sackler School of Medicine, The Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Tel-Aviv University, Tel-Aviv, Israel.
Haj-Yahia
Saleem
S
Solodeev
Inna
I
Levy
Yair
Y
Blank
Miri
M
Shoenfeld
Yehuda
Y
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D001761:Bleomycin / Q000633:toxicity; D024042:Collagen Type I / Q000187:drug effects* / Q000378:metabolism; D006909:Hydroxyproline / Q000187:drug effects / Q000378:metabolism; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D000903:Antibiotics, Antineoplastic; D024042:Collagen Type I; D016756:Immunoglobulins, Intravenous; D001761:Bleomycin; D006909:Hydroxyproline