Endocrine and Local IGF-I in the Bony Fish Immune System

Abstract

A role for GH and IGF-I in the modulation of the immune system has been under discussion for decades. Generally, GH is considered a stimulator of innate immune parameters in mammals and teleost fish. The stimulatory effects in humans as well as in bony fish often appear to be correlated with elevated endocrine IGF-I (liver-derived), which has also been shown to be suppressed during infection in some studies. Nevertheless, data are still fragmentary. Some studies point to an important role of GH and IGF-I particularly during immune organ development and constitution. Even less is known about the potential relevance of local (autocrine/paracrine) IGF-I within adult and developing immune organs, and the distinct localization of IGF-I in immune cells and tissues of mammals and fish has not been systematically defined. Thus far, IGF-I has been localized in different mammalian immune cell types, particularly macrophages and granulocytes, and in supporting cells, but not in T-lymphocytes. In the present study, we detected IGF-I in phagocytic cells isolated from rainbow trout head kidney and, in contrast to some findings in mammals, in T-cells of a channel catfish cell line. Thus, although numerous analogies among mammals and teleosts exist not only for the GH/IGF-system, but also for the immune system, there are differences that should be further investigated. For instance, it is unclear whether the primarily reported role of GH/IGF-I in the innate immune response is due to the lack of studies focusing on the adaptive immune system, or whether it truly preferentially concerns innate immune parameters. Infectious challenges in combination with GH/IGF-I manipulations are another important topic that has not been sufficiently addressed to date, particularly with respect to developmental and environmental influences on fish growth and health.

Keywords: GH; IGF; TNF-α; adaptive immune system; head kidney; innate immune system; lymphocytes; phagocytes; receptor; spleen.

Figure 1

Detection of IGF-I in channel catfish (I. punctatus) and rainbow trout (O. mykiss) leukocytes. (a,b) IGF-I mRNA and peptide in I. punctatus T-cell line G14D using (a) PCR and (b) immunocytochemistry. (a) Agarose gels of real-time PCR products confirming the presence of IGF-I mRNA (bands 2–4) at the expected size (73 bp) and reference gene 18S rRNA (bands 5–6) at the expected size (85 bp). Bands 1 and 7: molecular weight marker. (b) The majority of the T-cells show IGF-I immunoreactive material (brown color) within the cytoplasm. Nuclei counterstained with haematoxylin. Bar: 60 µm. (c) Head kidney leukocytes freshly isolated from rainbow trout were adjusted to 1 × 10⁷ cells/mL, incubated with mouse mAb against rainbow trout granulocytes (mAbQ4E; [56]) visualized with a Texas red-coupled anti-mouse antibody as previously described [54]. Subsequently, cells were fixed for intracellular labeling for IGF-I using the same antiserum as in (b) followed by a FITC-coupled anti rabbit antibody for double immunofluorescence of IGF-I (green) in phagocytic cells (red, arrow). Note the small cells immunoreactive for IGF-I, which do not express the granulocyte marker (single arrowheads) and the large cell immunoreactive for the granulocyte marker, but without immunoreactivity for IGF-I (double arrow heads). Bar: 30 µm.