I had to check out histamines and MS a little. There does appear to be some current research related to this:
Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1867-72. Epub 2003 Feb 7.
Multiple elements of the allergic arm of the immune response modulate autoimmune demyelination.
Pedotti R, DeVoss JJ, Youssef S, Mitchell D, Wedemeyer J, Madanat R, Garren H, Fontoura P, Tsai M, Galli SJ, Sobel RA, Steinman L.
Department of Neurology and Neurological Science, Stanford University Medical Center, Stanford, CA 94305, USA.
Analysis of mRNA from multiple sclerosis lesions revealed increased amounts of transcripts for several genes encoding molecules traditionally associated with allergic responses, including prostaglandin D synthase, histamine receptor type 1 (H1R), platelet activating factor receptor, Ig Fc epsilon receptor 1 (Fc epsilon RI), and tryptase. We now demonstrate that, in the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), mediated by T helper 1 (Th1) T cells, histamine receptor 1 and 2 (H1R and H2R) are present on inflammatory cells in brain lesions. Th1 cells reactive to myelin proteolipid protein expressed more H1R and less H2R than Th2 cells. Pyrilamine, an H1R antagonist, blocked EAE, and the platelet activating factor receptor antagonist CV6209 reduced the severity of EAE. EAE severity was also decreased in mice with disruption of the genes encoding Ig Fc gamma RIII or both Fc gamma RIII and Fc epsilon RI. Prostaglandin D synthase and tryptase transcripts were elevated in EAE brain. Taken together, these data reveal extensive involvement of elements of the immune response associated with allergy in autoimmune demyelination. The pathogenesis of demyelination must now be viewed as encompassing elements of both Th1 responses and "allergic" responses.
Int J Immunopathol Pharmacol. 2005 Oct-Dec;18(4):771-8.
A pilot, open label, clinical trial using hydroxyzine in multiple sclerosis.
Logothetis L, Mylonas IA, Baloyannis S, Pashalidou M, Orologas A, Zafeiropoulos A, Kosta V, Theoharides TC.
Department of Neurology, Aristotle University, AHEPA Hospital, Thessaloniki, Greece.
Multiple sclerosis (MS) is an autoimmune disorder of myelin destruction. Blood-brain-barrier (BBB) disruption precedes pathological or clinical findings and could involve mediators from perivascular brain mast cells, such as histamine and vascular endothelial growth factor (VEGF). Mast cells could be activated by many triggers, including acute stress that has been correlated with MS exacerbations. We considered that the histamine-1 (H1) receptor antagonist hydroxyzine, which also partially inhibits brain mast cells and has anxiolytic properties, may reduce MS symptoms. This open label, pilot, clinical trial investigated the effect on MS of an oral solution of hydroxyzine (100 mg per day), together with caffeine (200 mg per day) to reduce sedation. Twenty patients (8 males; 12 females) with relapsing-remitting or relapsing-progressive MS completed the study (12 +/- 1 months) and were evaluated using disability scales. Most patients on hydroxyzine (75%) remained stable or improved neurologically and all but one showed improved mood. Hydroxyzine could be used as an adjuvant in MS, but the small number of patients enrolled and the short duration of the study precludes any definitive conclusions. A double-blind, placebo-controlled study is warranted.
J Immunol. 2006 Jan 1;176(1):17-26.
A key regulatory role for histamine in experimental autoimmune encephalomyelitis: disease exacerbation in histidine decarboxylase-deficient mice.
Musio S, Gallo B, Scabeni S, Lapilla M, Poliani PL, Matarese G, Ohtsu H, Galli SJ, Mantegazza R, Steinman L, Pedotti R.
Immunology and Muscular Pathology Unit, National Neurological Institute "C. Besta," Milan, Italy.
Histamine can modulate the cytokine network and influence Th1 and Th2 balance and Ab-isotype switching. Thus, pharmacological blockade or genetic deletion of specific histamine receptors has been shown to reduce the severity of experimental autoimmune encephalomyelitis (EAE), a prototypic Th1-mediated disease with similarities to human multiple sclerosis. To study the comprehensive contribution of endogenous histamine to the expression of EAE, we attempted to induce EAE in histidine decarboxylase-deficient mice, which are genetically unable to make histamine. In this study, we show that EAE is significantly more severe in HDC-/-, histamine-deficient mice, with diffuse inflammatory infiltrates, including a prevalent granulocytic component, in the brain and cerebellum. Unlike splenocytes from wild-type mice, splenocytes from HDC-/- mice do not produce histamine in response to the myelin Ag, whereas production of IFN-gamma, TNF, and leptin are increased in HDC-/- splenocytes in comparison to those from wild-type mice. Endogenous histamine thus appears to regulate importantly the autoimmune response against myelin and the expression of EAE, in this model, and to limit immune damage to the CNS. Understanding which receptor(s) for histamine is/are involved in regulating autoimmunity against the CNS might help in the development of new strategies of treatment for EAE and multiple sclerosis.
Neurology. 2006 Feb 28;66(4):572-5.
Allergy, histamine 1 receptor blockers, and the risk of multiple sclerosis.
Alonso A, Jick SS, Hernan MA.
Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA. firstname.lastname@example.org
BACKGROUND: It is unclear whether allergic diseases are associated with multiple sclerosis (MS), but histamine 1 receptor blockers, used in the treatment of allergic conditions, decreased the severity of experimental autoimmune encephalomyelitis (an animal model of MS).
OBJECTIVE: To assess the association of allergy history and use of histamine 1 receptor blockers with the risk of MS.
METHODS: Using a case-control study nested in the United Kingdom-based General Practice Research Database cohort, the authors identified 163 incident cases of MS with at least 3 years of follow-up before their first symptoms (index date). Up to 10 controls matched to the cases by age, sex, general practice, and time in the cohort were selected. Previous history of allergic disease and use of histamine 1 receptor blockers in the 3 years before the index date were assessed through computerized medical records.
RESULTS: History of any allergic condition in the 3 years before the index date was not associated with MS risk (adjusted odds ratio [OR] 1.2, 95% CI 0.8 to 1.8 ). However, use of sedating histamine 1 receptor blockers was associated with decreased MS risk (adjusted OR 0.2, 95% CI 0.1 to 0.8 ).
CONCLUSION: These results do not support a strong link between allergic conditions and multiple sclerosis (MS) risk but suggest a possible beneficial effect of antihistamines on the onset of MS.