Alcohol-induced gastritis prevents oral tolerance induction in mice.
Despite several reports on the immunological relationship between inflammatory bowel diseases and immunoregulatory mechanisms in the gut, systematic studies addressing the impact of inflammatory processes in the gastric mucosa on events, such as oral tolerance, are still limited. Herein, we report the establishment of a novel murine model of gastritis induced by short-term administration of ethanol. The major immumological features of this clinical entity are characterized, as well as its impact on the induction of oral tolerance. Our data demonstrate that ethanol ingestion during 4 consecutive days triggered an acute inflammatory reaction in the stomach referred as ethanol-induced gastritis and characterized by hyperaemia, oedema and mixed mononuclear/polymorphonuclear cell infiltrate. Besides local immunological changes, such as high levels of gastric interleukin (IL)-4 and interferon (IFN)-gamma, systemic alterations are also observed, including increased IL-4 synthesis, enhanced levels of serum IgE and absence of IL-10 production by spleen cells. Moreover, ethanol-induced gastritis prevents oral tolerance induction to ovalbumin (OVA) as demonstrated by unaltered anti-OVA humoral and cellular immune responses in treated animals. Tissue eosinophilia after footpad immunization with OVA suggests that oral treatment with ethanol induced an allergic-type reaction. Taken together, our findings indicate that short-term ethanol ingestion is associated with gastric inflammatory events able to break immunoregulatory mechanisms that maintain mucosal homeostasis and oral tolerance.
Andrade
M C
MC
Departamento de Bioquímica e Imunologia, ICB, UFMG, Belo Horizonte MG, Brazil.
Menezes
J S
JS
Cassali
G D
GD
Martins-Filho
O A
OA
Cara
D C
DC
Faria
A M C
AM
D000208:Acute Disease; D000284:Administration, Oral; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D005753:Gastric Mucosa / Q000276:immunology; D005756:Gastritis / Q000139:chemically induced* / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000473:pathology; D007108:Immune Tolerance / Q000187:drug effects*; D007111:Immunity, Cellular / Q000187:drug effects; D018928:Immunity, Mucosal; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology
D015847:Interleukin-4; D000431:Ethanol; D007371:Interferon-gamma; D010047:Ovalbumin