Abstract

Increased thymic weights have been reported in sheep selected for resistance to internal parasites and treatment with IGF-1 increases thymic and splenic weights in sheep, suggesting that IGF-1 may have a role in regulating immune function. This hypothesis was examined in four experiments using mice as a model. Expt 1 Unselected Swiss mice (n-24) were injected 2 x daily with 30 mg/d rhIGF-1 or saline for 26 days from 28 days of age. IGF-1 treatment increased spleen weight at a common body weight (118.2 vs 95.9, pooled standard error (PSE) = 6.2 mg, P<0.05), but did not affect thymic regression (thymic weights at the end of treatment: 85.5 vs 81.9, PSE = 4.0 mg). Expt 2 Unselected female Swiss mice (n=22, age = 84.8±0.8 days) were injected 3 x daily with 30 mg/d rhIGF-1 or saline for 17 days. IGF-1 treatment increased thymic weight at a common body weight (78.4 vs 58.0, PSE = 3.0 mg, P<0.01), but had little effect on splenic weight (180.1 vs 163.0, PSE = 7.5 mg, P>0.10), Expt 3 Histological sections of spleens from High (H), Control (C), and Low (L) IGF-1 selected mice at 30 (n=30) and 120 (n=35) days of age were analyzed for the density of megakaryocytes (precursor cells for thrombocytes), and the percentage of the area covered by white pulp (lymphatic tissue). L mice had, compared to C and H mice, lighter spleens (62.6 vs 76.8 vs 89.6, PSE = 5.3 mg, at 30d; 60.2 vs 109.5 vs 114.5, PSE = 7.4 mg, at 120d; P<0.05), and a lower density of megakaryocytes (9.2 vs 13.4 vs 14.7, PSE = 1.6 n/mm2, at 30d; 2.1 vs 13.9 vs 14.3, PSE = 2.0 n/mm2, at 120d; P<0.05), but were not different in the percentage of the area covered by white pulp (16.1 vs 14.1 vs 13.4, PSE = 1.3%, at 30d; 28.3 vs 23.1 vs 23.8, PSE = 2.4%, at 120d). Expt 4 Mice from the three IGF-1 selection lines (n=13 vs n=13 vs n=14 for L vs C vs H, age=86.8±2.3 days) showed no difference in spleen weights (110.8 vs 137.4 vs 139.0, PSE = 11.8 mg; P>0.10). In response to an antigenic challenge with sheep red blood cells (SRBC), there was a small effect (P=0.10) of selection line on the number of plaque-forming (immunoglobulin M (IgM)- producing) cells (PFC) per spleen (880x103 vs 954x103 vs 1187x103, PSE = 130x103), but the differences in anti-SRBC antibody titres (IgM) in the plasma (10.8 vs 11.1 vs 11.7, PSE = 0.6) were not significant. It is concluded that IGF-1 affects splenic and thymic weights independently, that it influences the density of megakaryocytes in the spleen, and that it has an effect on the number of PFC per spleen in response to a SRBC challenge. However, the biological significance of these effects is still to be established.

B, Kuhn Sherlock, PCH Morel, JM Mathis, HT Blair, SN McCutcheon, J Marbrook, BH Breier, and PD Gluckman

Proceedings of the New Zealand Society of Animal Production, Volume 54, , 5-8, 1994