Horm Metab Res 2002; 34(8): 460-465
DOI: 10.1055/s-2002-33596
Original Clinical

© Georg Thieme Verlag Stuttgart · New York

High Concentrations of Procalcitonin but Not Mature Calcitonin in Normal Human Milk

J.  Struck 1 , P.  de Almeida 2 , A.  Bergmann 1 , N.  G.  Morgenthaler 1
  • 1Research Laboratories, B.R.A.H.M.S AG, Biotechnology Center Hennigsdorf, Hennigsdorf, Germany
  • 2Department of Obstetrics, Krankenhaus Neukölln, Berlin, Germany
Further Information

Publication History

Received: 6 December 2001

Accepted after revision: 25 April 2002

Publication Date:
25 September 2002 (online)

Abstract

Procalcitonin (PCT) is one of the precursors in the synthesis of calcitonin in thyroidal C-cells and other neuroendocrine cells. PCT and other calcitonin precursors in serum are present at less than 50 pg/ml in healthy individuals, but are highly elevated in serum where conditions leading to systemic inflammatory response syndrome or sepsis prevail. We measured PCT concentrations in milk and serum samples taken from 9 healthy women after delivery. PCT concentrations were below 10 pg/ml in serum samples, but were more than 100 times as high in the corresponding milk samples. PCT in milk reached a maximum within the early days after delivery, with a median peak concentration of 2310 pg/ml (range 223 - 4224 pg/ml) at day one and 2442 pg/ml (range 952 - 4488 pg/ml) at day two, then declining over the next days to a median concentration of 747 pg/ml (range 443 - 1656 pg/ml) at day 10 (p = 0.012, by Friedman ANOVA). PCT values reached a steady state of 504 pg/ml median value. Mature calcitonin values measured in parallel with a specific assay were not above the normal range of 10 pg/ml in any samples measured. The strong discrepancy between serum and milk PCT suggests that PCT (but not mature calcitonin) is synthesised in the breast of healthy mothers after delivery. The precise mechanism and the physiological relevance are unclear. Since PCT levels increase drastically in serum from patients suffering from sepsis and related conditions, and since PCT has been ascribed a pro-inflammatory function, we propose that milk PCT might contribute to the activation of the developing neonatal immune system. Similar speculations were proposed for a variety of other pro-inflammatory cytokines, which had comparable kinetics in human milk.

References

  • 1 Becker K L, Müller B, Nylen E, Cohen R, Silva O, Snider R. Calcitonin gene family of peptide. In: Becker, KL (ed) Principles and Practice of Endocrinology and Metabolism. Philadelphia; J. B. Lippincott 2001: 520-534
  • 2 Assicot M, Gendrel D, Carsin H, Raymond J, Guilbaud J, Bohuon C. High serum procalcitonin concentrations in patients with sepsis and infection.  Lancet. 1993;  341 515-518
  • 3 Rau B, Steinbach G, Gansauge F, Mayer J M, Grunert A, Beger H G. The potential role of procalcitonin and interleukin 8 in the prediction of infected necrosis in acute pancreatitis.  Gut. 1997;  41 832-840
  • 4 Nylen E S, O'Neill W, Jordan M H, Snider R H, Moore C F, Lewis M, Silva O L, Becker K L. Serum procalcitonin as an index of inhalation injury in burns.  Horm Metab Res. 1992;  24 439-443
  • 5 Mimoz O, Benoist J F, Edouard A R, Assicot M, Bohuon C, Samii K. Procalcitonin and C-reactive protein during the early posttraumatic systemic inflammatory response syndrome.  Intensive Care Med. 1998;  24 185-188
  • 6 Dandona P, Nix D, Wilson M F, Aljada A, Love J, Assicot M, Bohuon C. Procalcitonin increase after endotoxin injection in normal subjects.  J Clin Endocrinol Metab. 1994;  79 1605-1608
  • 7 Gendrel D, Assicot M, Raymond J, Moulin F, Francoual C, Badoual J, Bohuon C. Procalcitonin as a marker for the early diagnosis of neonatal infection.  J Pediatr. 1996;  128 570-573
  • 8 Snider R H Jr, Nylen E S, Becker K L. Procalcitonin and its component peptides in systemic inflammation: Immunochemical characterization.  J Investig Med. 1997;  45 552-560
  • 9 Whang K T, Steinwald P M, White J C, Nylen E S, Snider R H, Simon G L, Goldberg R L, Becker K L. Serum calcitonin precursors in sepsis and systemic inflammation.  J Clin Endocrinol Metab. 1998;  83 3296-3301
  • 10 Muller B, Becker K L, Schachinger H, Rickenbacher P R, Huber P R, Zimmerli W, Ritz R. Calcitonin precursors are reliable markers of sepsis in a medical intensive care unit.  Crit Care Med. 2000;  28 977-983
  • 11 Morgenthaler N G, Struck J, Fischer-Schulz C, Bergmann A. Sensitive immunoluminometric assay for the detection of procalcitonin.  Clin Chem. 2002;  48 788-790
  • 12 Assumma M, Signore F, Pacifico L, Rossi N, Osborn J F, Chiesa C. Serum procalcitonin concentrations in term delivering mothers and their healthy offspring: A longitudinal study.  Clin Chem. 2000;  46 1583-1587
  • 13 Bucht E, Arver S, Sjoberg H E, Low H. Heterogeneity of immunoreactive calcitonin in human milk.  Acta Endocrinol (Copenh). 1983;  103 572-576
  • 14 Arver S, Bucht E, Sjoberg H E. Calcitonin-like immunoreactivity in human milk, longitudinal alterations and divalent cations.  Acta Physiol Scand. 1984;  122 461-464
  • 15 Morgenthaler N G, Struck J, Fischer-Schulz C, Seidel-Mueller E, Beier W, Bergmann A. Detection of procalcitonin (PCT) in healthy controls and patients with local infection by a sensitive ILMA.  Clin Lab. 2002;  48 263-270
  • 16 Bucht E, Telenius-Berg M, Lundell G, Sjoberg H E. Immunoextracted calcitonin in milk and plasma from totally thyroidectomized women. Evidence of monomeric calcitonin in plasma during pregnancy and lactation.  Acta Endocrinol (Copenh). 1986;  113 529-535
  • 17 Bucht E, Sjoberg H E. Evidence for precursors of calcitonin/PDN 21 in human milk.  Regul Pept. 1987;  19 65-71
  • 18 Reinhart K, Karzai W, Meisner M. Procalcitonin as a marker of the systemic inflammatory response to infection.  Intensive Care Med. 2000;  26 1193-1200
  • 19 Nylen E S, Whang K T, Snider R H, Steinwald P M, White J C, Becker K L. Mortality is increased by procalcitonin and decreased by an antiserum reactive to procalcitonin in experimental sepsis.  Crit Care Med. 1998;  26 1001-1006
  • 20 Udall J N, Pang K, Fritze L, Kleinman R, Walker W A. Development of gastrointestinal mucosal barrier. I. The effect of age on intestinal permeability to macromolecules.  Pediatr Res. 1981;  15 241-244
  • 21 Muller B, White J C, Nylen E S, Snider R H, Becker K L, Habener J F. Ubiquitous expression of the calcitonin-I gene in multiple tissues in response to sepsis.  J Clin Endocrinol Metab. 2001;  86 396-404
  • 22 Bernt K M, Walker W A. Human milk as a carrier of biochemical messages.  Acta Paediatr Suppl. 1999;  88 27-41
  • 23 Garofalo R P, Goldman A S. Expression of functional immunomodulatory and anti-inflammatory factors in human milk.  Clin Perinatol. 1999;  26 361-377
  • 24 Goldman A S, Chheda S, Garofalo R, Schmalstieg F C. Cytokines in human milk: Properties and potential effects upon the mammary gland and the neonate.  J Mammary Gland Biol Neoplasia. 1996;  1 251-258
  • 25 Garofalo R P. Cytokines, chemokines, and colony-stimulating factors in human milk: The 1997 update.  Biol Neonate. 1998;  74 134-142
  • 26 Goldman A S, Chheda S, Garofalo R. Evolution of immunologic functions of the mammary gland and the postnatal development of immunity.  Pediatr Res. 1998;  43 155-162
  • 27 Jones C A. Breast milk as an alternative source of cytokines for offspring.  Clin Exp Allergy. 2000;  30 599-601
  • 28 Hawkes J S, Bryan D L, James M J, Gibson R A. Cytokines (IL-1beta, IL-6, TNF-alpha, TGF-beta1, and TGF-beta2) and prostaglandin E2 in human milk during the first three months postpartum.  Pediatr Res. 1999;  46 194-199

Dr. N. G. Morgenthaler

Research Laboratories · B.R.A.H.M.S AG · Biotechnology Center Hennigsdorf

Neuendorfstr. 25 · 16761 Hennigsdorf · Germany

Phone: + 49 (3302) 883 450

Fax: + 49 (3302) 883 451

Email: n.morgenthaler@brahms.de