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Nasal administration of multiple antigens suppresses experimental autoimmune myasthenia gravis, encephalomyelitis and neuritis.
J Neurol Sci. 1998 Feb 18; 155(1):1-12.JN

Abstract

Oral tolerization with acetylcholine receptor (AChR) and myelin basic protein (MBP) prior to immunization with AChR+MBP+ complete Freund's adjuvant (CFA) alleviated clinical signs of experimental autoimmune myasthenia gravis (EAMG)+experimental allergic encephalomyelitis (EAE) and AChR- or MBP-specific T and B cell responses. Tolerance induced via the nasal route needs much less tolerogen and may still be as effective as oral tolerance induction. We now immunized Lewis rats with AChR+MBP+bovine peripheral nerve myelin (BPM)+CFA, which resulted in a multiphasic clinical picture with a combination of clinical signs of the EAMG+EAE+experimental allergic neuritis (EAN), accompanied by massive macrophage infiltrations in sections of muscle, spinal cord and sciatic nerve, and strong T and B cell responses to AChR, MBP and BPM in lymphoid organs. Nasal administration of microg doses of AChR+MBP+BPM prior to immunization with a mixture of these antigens+CFA effectively suppressed the incidence and severity of clinical disease, reduced macrophage infiltrations in sections of muscle, spinal cord and sciatic nerve, and down-regulated autoreactive T cell responses to the three antigens in lymphoid organs. Numbers of AChR-, MBP-, BPM-reactive Th1 type of cytokine interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha mRNA expression in lymph node cells were markedly suppressed, while transforming growth factor-beta (TGF-beta) mRNA expression was upregulated from nasally tolerized rats, suggesting an active suppression mechanism may act partly in the induction of tolerance. The results implicate the possibility to establish multiple autoantigen-based vaccination for the prevention of autoimmune diseases in humans.

Authors+Show Affiliations

Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9562316

Citation

Shi, F D., et al. "Nasal Administration of Multiple Antigens Suppresses Experimental Autoimmune Myasthenia Gravis, Encephalomyelitis and Neuritis." Journal of the Neurological Sciences, vol. 155, no. 1, 1998, pp. 1-12.
Shi FD, Bai XF, Xiao BG, et al. Nasal administration of multiple antigens suppresses experimental autoimmune myasthenia gravis, encephalomyelitis and neuritis. J Neurol Sci. 1998;155(1):1-12.
Shi, F. D., Bai, X. F., Xiao, B. G., van der Meide, P. H., & Link, H. (1998). Nasal administration of multiple antigens suppresses experimental autoimmune myasthenia gravis, encephalomyelitis and neuritis. Journal of the Neurological Sciences, 155(1), 1-12.
Shi FD, et al. Nasal Administration of Multiple Antigens Suppresses Experimental Autoimmune Myasthenia Gravis, Encephalomyelitis and Neuritis. J Neurol Sci. 1998 Feb 18;155(1):1-12. PubMed PMID: 9562316.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nasal administration of multiple antigens suppresses experimental autoimmune myasthenia gravis, encephalomyelitis and neuritis. AU - Shi,F D, AU - Bai,X F, AU - Xiao,B G, AU - van der Meide,P H, AU - Link,H, PY - 1998/4/30/pubmed PY - 1998/4/30/medline PY - 1998/4/30/entrez SP - 1 EP - 12 JF - Journal of the neurological sciences JO - J. Neurol. Sci. VL - 155 IS - 1 N2 - Oral tolerization with acetylcholine receptor (AChR) and myelin basic protein (MBP) prior to immunization with AChR+MBP+ complete Freund's adjuvant (CFA) alleviated clinical signs of experimental autoimmune myasthenia gravis (EAMG)+experimental allergic encephalomyelitis (EAE) and AChR- or MBP-specific T and B cell responses. Tolerance induced via the nasal route needs much less tolerogen and may still be as effective as oral tolerance induction. We now immunized Lewis rats with AChR+MBP+bovine peripheral nerve myelin (BPM)+CFA, which resulted in a multiphasic clinical picture with a combination of clinical signs of the EAMG+EAE+experimental allergic neuritis (EAN), accompanied by massive macrophage infiltrations in sections of muscle, spinal cord and sciatic nerve, and strong T and B cell responses to AChR, MBP and BPM in lymphoid organs. Nasal administration of microg doses of AChR+MBP+BPM prior to immunization with a mixture of these antigens+CFA effectively suppressed the incidence and severity of clinical disease, reduced macrophage infiltrations in sections of muscle, spinal cord and sciatic nerve, and down-regulated autoreactive T cell responses to the three antigens in lymphoid organs. Numbers of AChR-, MBP-, BPM-reactive Th1 type of cytokine interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha mRNA expression in lymph node cells were markedly suppressed, while transforming growth factor-beta (TGF-beta) mRNA expression was upregulated from nasally tolerized rats, suggesting an active suppression mechanism may act partly in the induction of tolerance. The results implicate the possibility to establish multiple autoantigen-based vaccination for the prevention of autoimmune diseases in humans. SN - 0022-510X UR - https://www.unboundmedicine.com/medline/citation/9562316/Nasal_administration_of_multiple_antigens_suppresses_experimental_autoimmune_myasthenia_gravis_encephalomyelitis_and_neuritis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-510X(97)00232-3 DB - PRIME DP - Unbound Medicine ER -