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Antisecretory factor in inflammation and secretion disorders

Research group

Short description

Antisecretory factor (AF) is a 43 kD protein, expressed in most cells. AF regulates secretion and decreases inflammation. In a healthy person most AF is in an inactive form, but it can be activated through exposure to bacterial toxins or by intake of specific food components. The active sequence, responsible for the actions of AF, is a 8 as long peptide in the N-terminal part of the protein. A longer peptide, AF16, is more stable and useful for experimental work. Clinical studies have shown that an AF-activating diet is beneficial in a number of diseases in which inflammation and/or secretory disturbances are the main symptoms. The aim of Eva Jennische's project is to clarify the mechanism of action for AF and investigate how the positive effects of AF can be used clinically.

Antisecretory factor (AF) is a 43 kD protein which affects inflammation and secretory processes. AF was identified and cloned in our group (1995). AF is expressed in most cells and is also present in plasma and breast milk. In a healthy person most of the AF is present in an inactive form. AF is activated when the intestine is exposed to diarrhea inducing enterotoxic agents and the increased AF-activity contributes to the normalization of the intestinal secretion. AF can be considered to be a part of the innate immune system. AF can also be activated through intake of specific food components. We have shown that a food supplement, Special Processed Cereals (SPC-Flakes®), increases AF-activity in plasma. Alternatively a high AF level can be achieved through intake of an egg drink made from egg yolk with a high AF-content (Salovum®). Patients with chronic illnesses och small infants can have difficulties increasing the endogenous AF-activity as a response to e.g. diarrhea and AF therapy can be beneficial in these cases. Clinical studies have shown that AF-therapy can reduce symptoms in patients with inflammatory bowel disease, infant diarrhea and diarrhea of endocrine origin. A positive effect has also been documented in Meniere’s disease. SPC-flakes and Salovum are food supplements and have been classified by Läkemedelsverket as “Food for Special Medical Purposes”. They can be included in the diet and no adverse effects in the medical sense have so far been noticed.

The anti-secretory and anti-inflammatory active part of AF is a 8 amino acid long peptide at the N-terminal part. A longer peptide, AF16, including the active sequence is more stable and therefore suitable for experimental work.

AF16 given intranasally or intravenously decreases the interstitial tissue pressure in experimental solid tumors. A decrease tissue pressure could increase blood flow to the tumor and thereby increase penetration of chemotherapeutics and improve the effect of the treatment. So far this hypothesis has not been tested clinically.

In a model of traumatic brain injury in rats we found that AF16 significantly decreased the trauma induced intracranial pressure. These results led to a clinical study at the department of neurosurgery SS/SU in which patients with traumatic brain injury was given Salovum®, as a complement to routine treatment. So far five patients have been treated with promising results.

Our clinical studies show that AF-therapy is beneficial as a complement treatment in a number of common diseases. However, the mechanism of action for the effects of AF is still not known. In order to increase the confidence in this therapy it is of importance to clarify the mechanism of action for AF.

Group members

Ivar Lönnroth
Stefan Lange

Collaborations

Chalmers, Per Malmberg
Neurokirurgen SS/SU, Kliment Gatzinsky
Karolinska Institutet/KS, Anna Gustafsson
Uppsala Akademiska sjukhus, Peter Nygren