Differential induction of cutaneous TNF-alpha and IL-6 by topically applied chemicals.
BACKGROUND
Increasing evidence shows that contact allergens and skin irritants can induce or upregulate the cutaneous expression of cytokines, including those that are required for the initiation of immune responses and which participate in inflammatory reactions.


OBJECTIVE
The present investigation compared the ability of the skin allergens oxazolone and 2,4-dinitrochlorobenzene (DNCB) and the skin irritant benzalkonium chloride (BZC) to stimulate the cutaneous expression of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in mice.


RESULTS
Each chemical tested induced the dose-dependent production of IL-6 with similar kinetic profiles. BZC was less effective at provoking increases in this cytokine; concentrations (1%) that caused marked edema failed to stimulate significant changes in IL-6 expression. Under conditions of topical exposure in which each of these chemicals caused a vigorous inflammatory response in the skin, as measured by induced edema and the increased production of IL-6, only oxazolone and DNCB stimulated expression of TNF-alpha. The failure of BZC to initiate TNF-alpha production in the skin was not attributable to inhibition of the bioassay used to measure this cytokine and was apparently independent of the stimulation by this chemical of TNF-alpha inhibitory factors.


CONCLUSIONS
These data indicate that not all chemicals that have the ability to cause skin irritation and cutaneous inflammation will elicit detectable TNF-alpha responses and that characterization of cutaneous irritants and allergens on the basis of induced cytokine expression patterns in the skin must be approached with caution.
Holliday
M R
MR
Zeneca Central Toxicology Laboratory, Macclesfield, Cheshire, UK.
Corsini
E
E
Smith
S
S
Basketter
D A
DA
Dearman
R J
RJ
Kimber
I
I
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects; D000279:Administration, Cutaneous; D000485:Allergens / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D001548:Benzalkonium Compounds / Q000008:administration & dosage / Q000009:adverse effects; D016207:Cytokines / Q000096:biosynthesis; D004137:Dinitrochlorobenzene / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis*; D007509:Irritants / Q000008:administration & dosage / Q000009:adverse effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D010081:Oxazolone / Q000008:administration & dosage / Q000009:adverse effects; D011310:Preservatives, Pharmaceutical / Q000008:administration & dosage / Q000009:adverse effects; D012867:Skin / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D015854:Up-Regulation
D000276:Adjuvants, Immunologic; D000485:Allergens; D001548:Benzalkonium Compounds; D016207:Cytokines; D004137:Dinitrochlorobenzene; D018836:Inflammation Mediators; D015850:Interleukin-6; D007509:Irritants; D011310:Preservatives, Pharmaceutical; D014409:Tumor Necrosis Factor-alpha; D010081:Oxazolone