Sulfur mustard induces immune sensitization in hairless guinea pigs.
Sulfur mustard (SM, bis-(2-chloroethyl) sulfide) is a well known chemical warfare agent that may cause long-term debilitating injury. Because of the ease of production and storage, it has a strong potential for chemical terrorism; however, the mechanism by which SM causes chronic tissue damage is essentially unknown. SM is a potent protein alkylating agent, and we tested the possibility that SM modifies cellular antigens, leading to an immunological response to "altered self" and a potential long-term injury. To that end, in this communication, we show that dermal exposure of euthymic hairless guinea pigs induced infiltration of both CD4(+) and CD8(+) T cells into the SM-exposed skin and strong upregulated expression of proinflammatory cytokines and chemokines (TNF-alpha, IFN-gamma, and IL-8) in distal tissues such as the lung and the lymph nodes. Moreover, we present evidence for the first time that SM induces a specific delayed-type hypersensitivity response that is associated with splenomegaly, lymphadenopathy, and proliferation of cells in these tissues. These results clearly suggest that dermal exposure to SM leads to immune activation, infiltration of T cells into the SM-exposed skin, delayed-type hypersensitivity response, and molecular imprints of inflammation in tissues distal from the site of SM exposure. These immunological responses may contribute to the long-term sequelae of SM toxicity.
Mishra
Neerad C
NC
Lovelace CounterACT Research Center of Excellence, Lovelace Respiratory Research Institute, 2425 Ridgecrest Dr. SE, Albuquerque, NM 87108, USA.
Rir-sima-ah
Jules
J
March
Thomas
T
Weber
Waylon
W
Benson
Janet
J
Jaramillo
Richard
R
Seagrave
Jean-Clare
JC
Schultz
Gregory
G
Grotendorst
Gary
G
Sopori
Mohan
M
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D002619:Chemical Warfare Agents / Q000633:toxicity*; D016207:Cytokines / Q000187:drug effects / Q000276:immunology; D006168:Guinea Pigs; D006968:Hypersensitivity, Delayed / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology; D008168:Lung / Q000187:drug effects; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology; D008297:Male; D009151:Mustard Gas / Q000633:toxicity*; D012867:Skin / Q000187:drug effects* / Q000276:immunology
D002619:Chemical Warfare Agents; D016207:Cytokines; D009151:Mustard Gas