Abstract
Neonates are vulnerable to infections because of their immature immunity. IGF-I has been reported to have profound positive effects on immune function. In this study, we investigated the effects of IGF-I on neonatal immunity. The production of IL-2, IL-4, and interferon-γ in phytohemagglutinin (PHA)-stimulated neonatal mononuclear cells (MNC) was significantly decreased when compared with that of adults. IGF-I alone induced a high level of IL-6 mRNA expression and protein production in neonatal MNC. IGF-I significantly increased mRNA expression and protein production of both IL-6 and interferon-γ but had no influence on that of IL-2 and IL-4 in PHA-stimulated neonatal MNC. Moreover, it increased neonatal interferon-γ production in PHA-stimulated MNC to a level similar to that of adults. IGF-I could further enhance the mRNA expression of lymphocyte-activation gene 3, which is associated with interferon-γ production and differentiation of T-helper 1 lymphocytes, in PHA-stimulated neonatal MNC. These results suggest IGF-I could promote maturation of neonatal T cells, and its potential use to enhance neonatal immunity deserves further study.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- IFN-γ:
-
interferon-γ
- Th:
-
T-helper cells
- LAG-3:
-
lymphocyte-activation gene 3
- MNC:
-
mononuclear cells
- GAPDH:
-
glyceraldehyde phosphate dehydrogenase
- PHA:
-
phytohemagglutinin
- RT:
-
reverse transcription
- TNF:
-
tumor necrosis factor
References
Wilson CB, Lewis DB, English BK 1991 T cell development in the fetus and neonate. Adv Exp Med Biol 310: 17–27
Lewis DB, Yu CC, Meyer J, English BK, Kahn SJ, Wilson CB 1991 Cellular and molecular mechanisms for reduced interleukin 4 and interferon-γ production by neonatal T cells. J Clin Invest 87: 194–202
Wilson CB, Lewis DB 1990 Basis and implications of selectively diminished cytokine production in neonatal susceptibility to infection. Rev Infect Dis 12: S410–S420
Tucci A, Mouzaki A, James H, Bonnefoy JY, Zuber RH 1991 Are cord blood B cells functionally mature?. Clin Exp Immunol 84: 389–394
Kovarik J, Siegrist C-A 1998 Immunity in early life. Immunol Today 19: 150–152
Clement LR, Vink PE, Bradley G 1990 Novel immunoregulatory functions of phenotypically distinct subpopulations of CD4+ cells in the human neonate. J Immunol 145: 102–108
Kooijman R, Hooghe-Peters EL, Hooghe R 1996 Prolactin, growth hormone, insulin-like growth factor-I in the immune system. Adv Immunol 63: 377–454
Bjerknes R, Aarskog D 1995 Priming of human polymorphonuclear neutrophilic leukocytes by insulin-like growth factor I: increased phagocytic capacity, complement receptor expression, degranulation, and oxidative burst. J Clin Endocrinol Metab 80: 1948–1955
Kooijman R, Willems M, de Haas CJC, Rijkers GT, Schuurmans ALG, van Buul-Offers SC, Heijnen CJ, Zeger BJM 1992 Expression of type I insulin-like growth factors on human peripheral blood mononuclear cells. Endocrinology 131: 2244–2250
Bidlingmaier M, Auernhammer CJ, Feldmeier H, Strasburger CJ 1997 Effect of growth hormone and insulin-like growth factor I binding to natural killer cells. Acta Paediatr Suppl 423: 80–81
Kimata H, Yoshida A 1994 Effect of growth hormone and insulin-like growth factor-I on immunoglobulin production by and growth of human B cells. J Clin Endocrinol Metab 78: 635–641
Kimata H, Yoshida A 1994 Differential effect of growth hormone and insulin-like growth factor-I, insulin-like growth factor-II, and insulin on Ig production and growth in human plasma cells. Blood 83: 1569–1574
Kimata H, Fujimoto M 1994 Growth hormone and insulin-like growth factor I induce immunoglobulin production (Ig) E and IgG4 production by human B cells. J Exp Med 180: 727–732
Kooijman R, Willems M, Rijkers GT, Brinkman A, van Buul-Offers SC, Heijnen CJ, Zeger BJM 1992 Effects of insulin-like growth factors and growth hormone on the in vitro proliferation of T lymphocytes. J Neuroimmunol 38: 95–104
Roldan A, Charreau E, Schillaci R, Eugui EM, Allison AC 1989 Insulin-like growth factor-I increases the mitogenic response of human peripheral blood lymphocytes to phytohemagglutinin. Immunol Lett 20: 5–8
Tapson VF, Boni-Schnetzler M, Pilch MF, Center DM, Berman JS 1988 Structural and functional characterization of the human T lymphocyte receptor for insulin-like growth factor I in vitro. J Clin Invest 82: 950–957
Kelley KW, Arkins S, Minshall C, Liu Q, Dantzer R 1996 Growth hormone, growth factors and hematopoiesis. Horm Res 45: 38–45
LeRoith D, Yanowski J, Kaldjian EP, Jaffe ES, LeRoith T, Purdue K 1996 The effects of growth hormone and insulin-like growth factor I on the immune system of aged female monkeys. Endocrinology 137: 1071–1079
Gelato MC 1996 Aging and immune function: a possible role for growth hormone. Horm Res 45: 46–49
Juul A, Bang P, Thomas NT, Main K, Dalgaard P, Jorgensen K, Muller J, Hall K, Skakkebaek NE 1994 Serum insulin-like growth-I in 1030 healthy children, adolescents, and adults: relation to age, sex, stage of puberty, testicular size, and body mass index. J Clin Endocrinol Metab 78: 744–752
Lagoo-Deenadayalan S, Lagoo AS, Barber WH, Hardy KJ 1993 A standardized approach to PCR-based semiquantitation of multiple cytokine gene transcripts from small cell samples. Lymphokine Cytokine Res 12: 59–67
Odinot PT, Curfs JHAJ, Meis JFGM, Melchers WJG, Hoogkamp-Korstanje JAA 1998 Local expression of cytokine mRNA in spleen and Peyer's patches of rats is involved in resistance against infection with Yersinia enterocolitica. Cytokine 10: 206–212
Fresno M, Kopf M, Rivas L 1997 Cytokine and infectious diseases. Immunol Today 18: 56–58
Kruse A, Rink L, Rutenfranz I, Kolanczyk B, Kirchner H 1992 Interferon and lymphokine production by human placental and cord blood cells. J Interferon Cytokine Res 12: 113–117
Watson W, Oen K, Ramdahin R, Harman C 1991 Immunoglobulin and cytokine production by neonatal lymphocytes. Clin Exp Immunol 83: 169–174
Pastorelli G, Rousset F, Pene J, Peronne C, Roncarolo MG, Tovo PA, de Vires JE 1990 Cord blood B cells are mature in their capacity to switch to IgE-producing cells in response to interleukin-4 in vitro. Clin Exp Immunol 82: 114–119
Sautois B, Fillet G, Beguin Y 1997 Comparative cytokine production by in vitro stimulated mononucleated cells from cord blood and adult blood. Exp Hematol 25: 103–108
Andersson U, Andersson J, Lindfors A, Wagner K, Moller G, Heusser C 1990 Simultaneous production of interleukin 2, interleukin 4 and interferon-γ by activated human blood lymphocytes. Eur J Immunol 20: 1591–1596
Kruse A, Neustock P, Reuter M, Kirchner H 1993 T-cell surface molecular expression and interferon-γ production in human cord blood. J Interferon Res 13: 221–225
Kooijman R, Rijkers GT, Zegers BJM 1996 IGF-I potentiates interleukin-2 production in human peripheral T cells. J Endocrinol 149: 351–356
Tilg H, Dinarello AC, Mier JW 1997 IL-6 and APPs: anti-inflammatory and immunosuppressive mediators. Immunol Today 18: 428–432
Inoue T, Saito H, Fukushima R, Inabak T, Lin MT, Fukatsu K, Muto T 1995 Growth hormone and insulin-like growth factor I enhance host defense in a murine sepsis model. Arch Surg 130: 1115–1122
Hinton PS, Peterson CA, Lo HC, Yang H, McCarthy D, Ney DM 1995 Insulin-like growth factor-I enhances immune response in dexamethasone-treated or surgically stressed rats maintained with total parenteral nutrition. JPEN J Parenter Enteral Nutr 19: 444–452
De-Benedetti F, Alonzi T, Moretta A, Lazzaro D, Costa P, Poli V, Martini A, Ciliberto G, Fattori E 1997 Interleukin 6 causes growth impairment in transgenic mice through a decrease in insulin-like growth factor-I: a model for stunted growth in children with chronic inflammation. J Clin Invest 99: 643–650
Samstein B, Hoimes ML, Fan J, Frost RA, Gelato MC, Lang CH 1996 IL-6 stimulation of insulin-like growth factor binding protein (IGFBP)-1 production. Biochem Biophys Res Commun 228: 611–615
Romagnani S 1997 The Th1/Th2 paradigm. Immunol Today 18: 263–266
Allen JE, Maizels RM 1997 Th1-Th2: reliable paradigm or dangerous dogma?. Immunol Today 18: 387–392
Delespesse G, Demeure CE, Yang LP, Ohshima Y, Byun DG, Shu U 1997 In vitro maturation of naive human CD4+ T lymphocytes into Th1, Th2 effectors. Int Arch Allergy Immunol 113: 157–159
Constant SL, Bottomly K 1997 Induction of Th1 and Th2 CD4+ T cell responses: the alternative approaches. Annu Rev Immunol 15: 297–322
Chehimi J, Trinchieri G 1994 Interleukin-12: a bridge between innate resistance and adaptive immunity with a role in infection and acquired immunodeficiency. J Clin Immunol 14: 149–161
Lamont AG, Adorini L 1996 IL-12: a key cytokine in immune regulation. Immunol Today 17: 214–217
D'Andrea A, Rengaraju M, Valiante NM, Chehimi J, Kubin M, Aste M, Chan SH, Kobayashi M, Young D, Nickbarg E, Chizzonite R, Wolf SF, Trinchieri G 1992 Production of natural killer cell stimulatory factor (interleukin 12) by peripheral blood mononuclear cells. J Exp Med 176: 1387–1398
McKenzie SE, Kline J, Douglas SD, Polin RA 1993 Enhancement in vitro of the low interferon-γ production of leukocytes from human newborn infants. J Leukoc Biol 53: 691–696
Triebel F, Jitsukawa S, Baixeras E, Roman-Roman S, Genevee C, Viegas-Pequignot E, Hercend T 1990 LAG-3, a novel lymphocyte activation gene closely related to CD4. J Exp Med 171: 1393–1405
Baixeras E, Huard B, Miossec C, Jitsukawa S, Martin M, Hercend T, Hauffray C, Triebel F, Piatier-Tonneau D 1992 Characterization of the lymphocyte activation gene 3-encoded protein: a new ligand for human leukocyte antigen class II antigen. J Exp Med 176: 327–337
Annunziato F, Manetti R, Tomasevic L, Giudizi MG, Biagiotti R, Gianno V, Germano P, Mavilia C, Maggi E, Romagnani S 1996 Expression and release of LAG-3-encoded protein by human CD4+ T cells are associated with IFN-γ production. FASEB J 10: 769–775
Acknowledgements
The authors thank the staff from ward A6, Queen Mary Hospital, in facilitating the collection of cord blood.
Author information
Authors and Affiliations
Additional information
Supported by RGC Grant HKU 471/96 M from the Hong Kong Research Grant Council.
Rights and permissions
About this article
Cite this article
Tu, W., Cheung, PT. & Lau, YL. IGF-I Increases Interferon-γ and IL-6 mRNA Expression and Protein Production in Neonatal Mononuclear Cells. Pediatr Res 46, 748 (1999). https://doi.org/10.1203/00006450-199912000-00019
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/00006450-199912000-00019
This article is cited by
-
Serum IGF-1 in patients with rheumatoid arthritis: correlation with disease activity
BMC Research Notes (2022)
-
Acromegaly, inflammation and cardiovascular disease: a review
Reviews in Endocrine and Metabolic Disorders (2020)
-
Epigallocatechin-3-Gallate Suppresses IGF-I-Induced Lipogenesis and Cytokine Expression in SZ95 Sebocytes
Journal of Investigative Dermatology (2012)
-
Insulin-like growth factor I promotes cord blood T cell maturation through monocytes and inhibits their apoptosis in part through interleukin-6
BMC Immunology (2008)
-
Childhood obesity and insulin resistance in a Yucatan mini-piglet model: putative roles of IGF-1 and muscle PPARs in adipose tissue activity and development
International Journal of Obesity (2005)


