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Editorial

Bovine colostrum – Therapeutic synergism involving immuno-modulation, nutritional supplementation and antibacterial action?

A.M. Waaga-Gasser

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Volume 45 p. 191 - 192

Abstract

A.M. Waaga-Gasser

A.M. Waaga-Gasser
In this issue of the Journal, Struff and Sprotte review the pharmacology and clinical pharmacology of bovine colostrum preparations. Bovine colostrum has properties similar to human colostrum in stimulating the immune system and more than one of the many present constituents seems to be involved. Bovine colostrum preparations also have value as a nutritional supplement and the importance of this in regard to the pharmacological actions is becoming more clearly defined. The quality and safety of bovine colostrum are subjects of paramount importance. Heat treatment during manufacture can remove pathogens but can also impair efficacy. Thus, the material used in clinical investigations has to be carefully selected, processed and tested before use.

Bovine colostrum contains approximately 90 useful components, the most interesting of which are immune factors and growth factors. Colostrum is also a source of vitamins, minerals, amino acids, proteins, fats and carbohydrates for the newborn. The immune factors present include specific antibodies, immunoglobulins, proline-rich polypeptides, lactoferrin, cytokines and trypsin inhibitors, lysozyme, leukocytes, lactoperoxidases and lactalbumins [Thapa 2005]. There are at least four groups of immune-enhancing factors present including growth factors, immunoglobulins, a putative permeability fraction and a fraction containing enzymes and peptides [van Hooijdonk et al. 2000].

Bovine colostrum has therapeutic effects in a variety of chronic infections of bacterial, viral, parasitic and fungal origin but it has also been used as a nutritional supplement to treat chronic fatigue syndrome, infectious diarrhea, sinusitis and fibromyalgia where it boosts the immune responses of the patient. Immunoglobulins in bovine colostrum preparations are thought to bestow protection against enteric infections [Sarkar et al. 1998] and eradicate certain microbial agents in the human gastrointestinal tract, e.g. Cryptosporidium, Shigella and toxin-producing E. coli. Bovine colostrum also contains antibodies against E. coli, Salmonella, Candida and H.-pylori infections [Stephan et al. 1990] where the preparations may prevent H. pylori from attaching to the lipid-binding sites in the gastric mucosa.

Clinical and experimental studies have thrown light on the pathogenic role of endotoxin in Gram-negative sepsis (for review see [Beutler and Rietschel 2003]) and the putative beneficial effects of bovine colostrum in this disease. Severe sepsis, and probably most prolonged critical illnesses, exhibit a paradoxical combination of both an increased activation and a marked depression of the immune system. Sepsis involves an imbalance between pro- and anti-inflammatory mediators produced by toxin-activated inflammatory cells where both proinflammatory mediators as well as immune paralysis are deleterious to the patient. Monoclonal antibodies and antagonists targeted against toxins and mediators have been used to prevent an overshoot in proinflammatory effects but the results have been disappointing [Baumgartner 1991]. Intravenous immunoglobulins on the other hand can increase bactericidal activity in serum by virtue of the neutralizing (endotoxins and exotoxins) and opsonizing IgG and IgM antibodies present and the stimulation of phagocytosis. Mechanisms like these are thought to be responsible for the therapeutic properties of IgG-enriched colostral milk preparations in sepsis since Fitzal and colleagues [2001] could show that when given orally, these preparations attenuate endotoxemia by reducing the intraluminal endotoxin content, reducing bacterial growth, preserving the intestinal wall and preventing the breakdown of the mucosal barrier. Breakdown of the mucosal barrier is a common finding in hemorrhage and leads to hemorrhage-induced endotoxemia [Fitzal et al. 2001]. Orally administered immunoglobulins may inhibit bacterial translocation through the bowel wall in intensive care patients with enteric (Gram-negative) septic shock and the mechanisms involved have been the subject of recent discussion: firstly, the primary site of action of the active immunoglobulins is the upper GI-tract where the translocation of pathogens and their toxins is “blocked”. There are no other comparable therapeutic agents known which can both destroy microbial pathogens and neutralize concomitantly the toxic products of bacterial decay. Secondly, although the mechanism underlying these neutralizing processes is still unclear, the combination of distinct effector molecules and their well-known synergistic actions may have their origin in phylogenetic adaptation and the developments of complex defense mechanisms.

On the other hand, it is clear that bovine colostrum is not only a substance with immunological properties but it is also a natural product with characteristics of a balanced dietary supplement, i.e. it contains nutritional components which contribute to the anabolic, energy, vitamin and trace element requirements of the body. Although the duration of treatment with bovine colostrum and intake (dose-response relationships) have not yet been optimized, bovine colostrum preparations could become useful therapeutic agents in severe human diseases involving impairment of immune defense systems. References

Baumgartner JD. Immunotherapy with antibodies to core lipopolysaccharide: a critical appraisal. Infect Dis Clin North Am. 1991; 5: 915-927.
Beutler B, Rietschel ET. Innate immune sensing and its roots: the story of endotoxins. Nature Reviews/Immunology. 2003; 3: 169-176.
Fitzal F, Racz I, Hamar J, Redl H, Bahrami S. Immunoglobulin enriched colostral milk reduces gut-derived endotoxemia in a rat hemorrhage model. Eur J Trauma. 2001; 5: 257-263.
Sarkar SA, Casswall TH, Mahalanabis D et al. Successful treatment of rotavirus diarrhea in children with immunoglobulin from immunized bovine colostrum. Pediatr Infect Dis J. 1998; 17: 1149-1154.
Stephan W et al. Antibodies from colostrum in oral immunotherapy. J Clin Chem Biochem. 1990; 28: 19-23.
Thapa BR. Health factors in colostrum. Indian J Pediatr. 2005; 72: 579-581.
van Hoojidonk AC, Kussendrager KD, Steijns JM. In vivo antimicrobial and antiviral activity of components in bovine mild and colostrums involved in non-specific defence. Br J Nutr. 2000; 84 (S-1): 127-134. Correspondence to:
Prof. Dr. A.M. Waaga-Gasser Department of Surgery I, Molecular Oncology and Immunology, University of Würzburg, Oberdürrbacher Straße 61 97080 Würzburg, Germany
Email: [email protected]

Original Reserach

Oral immunoglobulin induces mononuclear cell apoptosis in patients suffering from idiopathic chronic pain syndrome: Results from a pilot study

A.M. Waaga-Gasser, M. Gasser, M. Stock, M. Grimm and G. Sprotte

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Volume 47 p. 421 - 433

Abstract

A.M. Waaga-Gasser¹, M. Gasser², M. Stock³, M. Grimm¹ and G. Sprotte³

¹Department of Surgery I, Molecular Oncology and Immunology, ²Department of Surgery I and ³Pain Relief Center, Department of Anaesthesia and Critical Care, University of Wuerzburg, Germany
Objective: The objective of this clinical pilot study was to examine the induction of apoptosis in mononuclear cells on treatment of patients with chronic pain syndrome with oral immunoglobulin produced from bovine colostrum (BCC). Design: The 4 patients suffering from chronic idiopathic pain (idiopathic facial pain, CRPS or fibromyalgia) who were enrolled in the study had previously successfully been treated with BCC (varying individual doses). Mononuclear cells from peripheral blood were analyzed for representative cytokines in the serum as well as by TUNEL-assay to detect apoptotic cellular events 14 days after the last treatment with BCC and 14 days after restarting the treatment protocol with BCC. The clinical response (pain and quality of life parameters using a visual analogue scale (VAS)) were determined regularly in each patient. Results: The findings showed a disturbed apoptosis homeostasis in 3 of the 4 patients. These results were accompanied by a relief of the pain symptoms. The 4th patient was found not to need any further analgetic treatment since she demonstrated only nonsignificant changes in her laboratory screening and immunological parameters and by the end of the study she was also completely free of pain (long-term treatment with BCC). Conclusions: In spite of the low patient number, the results were obtained with a sufficiently high degree of control because of the study design. The agreement of the clinical data with our laboratory measurements suggests that the induction of apoptotic events in mononuclear cells is the result of the dominant immunological effects of BCC treatment.Correspondence to:
Prof. Dr. G. Sprotte
Pain Relief Centre
Department of Anaesthesia and Critical Care
University of Wuerzburg
Josef-Schneider-Straße 6
97080 Wuerzburg, Germany
Email: [email protected]

Book Review

Handbook of Drug-Nutrient Interactions, 2nd Edition

R.W. Lissner and A.M. Waaga-Gasser

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Volume 48 p. 779 - 780

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