Physiology and pathology of an immunoendocrine feedback loop

doi:10.1016/0167-5699(88)91289-3

Immunology Today

Volume 9, Issue 6, 1988, Pages 163-165

Immunology Today

https://doi.org/10.1016/0167-5699(88)91289-3 Get rights and content

Abstract

Research in autoimmunity has tended to focus on lymphocytes and their products at the expense of other factors that also contribute to the development of disease. Here, Guido Kroemer and colleagues stress that aberrations in immunoendocrinological communication may also be involved in autoaggression. They propose that in the Obese strain of chickens with spontaneous autoimmune thyroiditis, a defect in the regulation of corticosterone by immune signals can be implicated in immune hyperreactivity.

References (30)

J.E. Blalock et al.
Immunol. Today
(1985)
A. Uehara et al.
Biochem. Biophys. Res. Commun.
(1987)
G. Aichinger et al.
Clin. Immunol. Immunopathol.
(1984)
H.O. Besedovsky et al.
Immunol. Today
(1983)
D.G. Payan et al.
Adv. Immunol.
(1987)
R.K. Cole et al.
Immunol. Today
(1985)
G. Wick et al.
Immunol. Lett.
(1987)
G. Wick et al.
Immunol. Rev.
(1986)
R. Faessler et al.
J. Immunol.
(1986)
K. Schauenstein et al.
J. Immunol.
(1987)

R.H. Waterston

Science

(1970)

H.O. Besedovsky et al.

Clin. Exp. Immunol.

(1985)

H. Besedovsky et al.

Science

(1986)

R. Sapolsky et al.

Science

(1987)

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RostrumPhysiology and pathology of an immunoendocrine feedback loop

Abstract

Immunol. Today

Biochem. Biophys. Res. Commun.

Clin. Immunol. Immunopathol.

Immunol. Today

Adv. Immunol.

Immunol. Today

Immunol. Lett.

Immunol. Rev.

J. Immunol.

J. Immunol.

Science

Clin. Exp. Immunol.

Science

Science

Rostrum
Physiology and pathology of an immunoendocrine feedback loop