3 MMR, inferferon gamma, & intestinal permeability

[Teresa Binstock]

New data indicate that, in many families, Crohn's disease may be due to
an infectious etiology, and increased intestinal permeability is a
familial marker (1). Similarly, increased intestinal permeability has been
reported in appx 40% of kids with autism (2). We note also that interferon
gamma (INFg) is the principle cytokine induced by the MMR given to human
children (3), and INFg is a factor that contributes to increases in
intestinal permeability (eg, 4-5).

Comment: the findings of Andy Wakefield et al exist amidst a goodly amount
of supporting data. As documented in two prior posts to bionet.immunology,
there is substantial evidence that measles (wild-type or vaccinal) impairs
immunity; and the citations in this post establish that, via the induction
of interferon gamma, the MMR is likely to augment tendencies towards
increased intestinal permeability.

Teresa

1. Peeters M et al. Clustering of increased small intestinal permeability
in families with Crohn's disease.  Gastroenterology.  113(3):802-7, 1997.
  BACKGROUND & AIMS: Small intestinal permeability is increased in a
  proportion of patients with Crohn's disease (CD) and a subset of their
  healthy relatives. A primary permeability defect was postulated in the
  pathogenesis of the disease. The aim of this study was to identify a
  possible genetic pattern in the distribution of CD and/or abnormal
  permeability. METHODS: Differential urinary excretion of lactulose and
  mannitol (L/ M) in complete CD families was determined. Controls included
  healthy families and families with ulcerative colitis. Pedigrees were used
  to compare the distribution of CD and/or increased permeability. RESULTS:
  The L/M was significantly increased in patients with CD. Seventeen of 67
  first-degree relatives (25%) had a ratio greater than the upper limit (P95
  = 0.0170). Permeability results of CD families showed a highly significant
  familial aggregation. The lack of a genetic pattern in relation with CD
  and occurrence of disturbed permeability especially within generation,
  points toward a shared environmental factor. Five of 14 healthy spouses
  (36%) of patients with CD had also an increased permeability, and
  prevalence of increased permeability was not higher in families with known
  familial occurrence (P = 0.85). CONCLUSIONS: This large family study
  confirms an increased permeability in a subset of healthy relatives of
  patients with CD. However, the absence of a typical family pattern and the
  high prevalence in spouses is in favor of a common nongenetic factor or a
  subclinical disease manifestation.

2. D'Eufemia P et al. Abnormal intestinal permeability in children with
autism.  Acta Paediatrica.  85(9):1076-9, 1996 Sep.
  We determined the occurrence of gut mucosal damage using the intestinal
  permeability test in 21 autistic children who had no clinical and
  laboratory findings consistent with known intestinal disorders. An altered
  intestinal permeability was found in 9 of the 21 (43%) autistic patients,
  but in none of the 40 controls. Compared to the controls, these nine
  patients showed a similar mean mannitol recovery, but a significantly
  higher mean lactulose recovery (1.64% +/- 1.43 vs 0.38% +/- 0.14; P <
  0.001). We speculate that an altered intestinal permeability could
  represent a possible mechanism for the increased passage through the gut
  mucosa of peptides derived from foods with subsequent behavioural
  abnormalities.

3. Pabst HF et al. Kinetics of immunologic responses after primary MMR
vaccination.  Vaccine.  15(1):10-4, 1997 Jan.
  To study the kinetics of humoral as well as cellular immunity to measles
  and to test for associated immunosuppression 124 12 month old children
  were studied twice, before routine MMR and either 14, 22, 30, or 38 days
  after vaccination...  Interferon-gamma was the principal cytokine 
  produced after primary measles immunization, suggesting primary measles
  immunization induces predominantly a TH1 type response.

4. Sanders SE et al. Assessment of inflammatory events in epithelial
permeability: a rapid screening method using fluorescein dextrans.
Epithelial Cell Biology.  4(1):25-34, 1995.
  Cultured intestinal epithelial monolayers serve as models for mechanistic
  studies of intestinal inflammation. One crucial aspect of epithelial
  function modulated by inflammation is permeability...  Exposure of
  intestinal epithelia to mucosal-derived lymphocytes or to soluble
  lymphocyte products (interferon-gamma, interleukin-4 or interleukin-13)
  increased FD flux in a dose-dependent fashion. Finally, studies of
  neutrophil transepithelial migration revealed qualitative and quantitative
  differences in FD flux depending on FD size. We conclude that in vitro
  transepithelial FD flux may be a useful tool to study aspects of
  intestinal permeability in health and in disease.

5. Unno N et al. Nitric oxide mediates interferon-gamma-induced
hyperpermeability in cultured human intestinal epithelial monolayers.
Critical Care Medicine.  23(7):1170-6, 1995 Jul.
  OBJECTIVE: Incubation with interferon-gamma has been shown to increase the
  permeability of cultured monolayers of intestinal epithelial cells...
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