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Disease states that affect intra-portal insulin levels by increasing insulin resistance causing compensatory intra-portal hyperinsulinemia or by decreasing pancreatic -cell insulin secretion causing intra-portal hypoinsulinemia results in changes to hepatic IGF-I synthesis and secretion, and consequently changes in GH levels via the negative feedback loop

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Additionally, chronic estradiol application promotes the expression of interleukin (IL)1, IL-6, IL-12p40, and Inducible nitric oxide synthase (iNOS) in macrophages following lipopolysaccharide (LPS) stimulation, further enhancing immune responses [105]