Macrophage migration inhibitory factor exhibits a pronounced circadian rhythm relevant to its role as a glucocorticoid counter-regulator.
In humans, maximal expression of T helper 1 cytokines coincide with the nocturnal nadir of plasma cortisol, whereas T helper 2 cytokine responses are dominant during day-time. The pro-inflammatory cytokine, macrophage migration inhibitory factor counter-regulates glucocorticoid-mediated immune suppression. To determine the relationship between cortisol and macrophage migration inhibitory factor, healthy volunteers had blood drawn hourly for 24 h for measurement of plasma cortisol and basal- and stimulated-macrophage migration inhibitory factor. Similar to cortisol, macrophage migration inhibitory factor peaked during the late morning whereas interferon-gamma, tumour necrosis factor-alpha, interleukin-1 and interleukin-12 demonstrated a nocturnal peak. After oral cortisone, plasma macrophage migration inhibitory factor rose 2-4-fold, whereas the other cytokines decreased. There was no correlation between cortisol during the insulin tolerance test and plasma macrophage migration inhibitory factor. The late morning peak of macrophage migration inhibitory factor, by antagonizing cortisol-mediated pro-inflammatory cytokine suppression may prolong the duration of early morning inflammation. These observations explain the beneficial role of macrophage migration inhibitory factor neutralization in models of inflammatory arthritis.
Petrovsky
Nikolai
N
Autoimmunity Research Unit, The Canberra Hospital, John Curtin School of Medical Research, Australian National University, Canberra, Australia. nikola.petrovsky@anu.edu.au
Socha
Luis
L
Silva
Diego
D
Grossman
Ashley B
AB
Metz
Christine
C
Bucala
Richard
R
D000328:Adult; D001427:Bacterial Toxins / Q000494:pharmacology; D002940:Circadian Rhythm; D016207:Cytokines / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007003:Hypoglycemia / Q000097:blood / Q000139:chemically induced; D007328:Insulin / Q000494:pharmacology; D007958:Leukocyte Count; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood* / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010902:Pituitary Gland / Q000276:immunology
D001427:Bacterial Toxins; D016207:Cytokines; D005938:Glucocorticoids; D007328:Insulin; D008263:Macrophage Migration-Inhibitory Factors; D006854:Hydrocortisone