Intradermal challenge with interleukin-8 causes tissue oedema and neutrophil accumulation in atopic and non-atopic human subjects.
BACKGROUND
Interleukin-8 (IL-8) is a cytokine with potent neutrophil chemotactic and activating properties and is active in inflammatory conditions in man. It has been identified in human inflammatory skin conditions where it is likely to be responsible for both neutrophil recruitment from the circulation and possibly T-lymphocyte chemoattraction. Studies in animals also suggest that IL-8 may augment skin oedema.


OBJECTIVE
To study the effects of intradermally administered IL-8 in humans on tissue oedema and cellular recruitment in atopic and non-atopic volunteers.


METHODS
Interleukin-8 (1.2 x 10(-7) M) in the presence and absence of histamine was administered by intradermal injection. Wheal and erythema area were measured at regular intervals and 3 h following challenge punch biopsies were taken for immunocytochemistry. Cellular infiltrate was measured by immunocytochemical identification of neutrophils, eosinophils and T-lymphocytes in glycol-methacrylate-embedded sections.


RESULTS
In the presence of histamine, IL-8 provoked a significantly greater wheal area when compared to that produced by histamine alone (P < 0.001). In the presence of histamine, IL-8 produced a significantly greater neutrophil infiltrate (P < 0.05), however, neither lymphocyte or eosinophil infiltration was found to be increased with IL-8 challenge. There was no difference observed between atopic and non-atopic subjects, nor were any effects of IL-8 demonstrated in the absence of histamine.


CONCLUSIONS
This study demonstrates that in human skin, IL-8 induces increased microvascular permeability and neutrophil infiltration, but not eosinophil or T-lymphocyte chemoattraction.
Douglass
J
J
Department of Immunopharmacology, Southampton General Hospital, UK.
Dhami
D
D
Bulpitt
M
M
Lindley
I J
IJ
Shute
J
J
Church
M K
MK
Holgate
S T
ST
D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000009:adverse effects; D002199:Capillary Permeability / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004487:Edema / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D004804:Eosinophils / Q000502:physiology; D006632:Histamine / Q000008:administration & dosage; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology / Q000503:physiopathology*; D007150:Immunohistochemistry; D007271:Injections, Intradermal; D016209:Interleukin-8 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000502:physiology*; D011994:Recombinant Proteins; D012871:Skin Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D013601:T-Lymphocytes / Q000502:physiology
D000485:Allergens; D016209:Interleukin-8; D011994:Recombinant Proteins; D006632:Histamine