In vitro heparan sulfate modulates the immune responses of normal and tumor-bearing mice.
Tumor-bearing (TB) patients and TB animal models show a wide array of immunologic deficits. Heparan sulfate (HS) has been shown to both improve immune cell proliferative responses and to induce Th1 cytokine responses in normal animals. These HS effects, if harnessed, would be of great benefit to TB patients. The present study focused on replicating previous HS-induced Th1 and proliferative response results as well as extrapolating the beneficial immunomodulatory effects to an experimental model derived from TB animals of Lewis lung cell carcinoma. Lewis Lung Carcinoma (LLC)-TB and control mouse splenocytes were assessed for proliferation and cytokine response to concanavalin A (Con A) with 1 and 3 days' exposure to HS. Our results found HS treatment stimulated splenocyte proliferation to Con A in control mice splenocytes after 1 and 3 days of treatment, although HS proliferative effects were not seen in unfractionated TB cultures. Furthermore, cytokine studies revealed normal splenocytes treated with HS had increased levels of both Th1 and Th2 cytokines. Surprisingly, HS treated TB-splenocytes showed suppressed cytokine levels. Of particular interest was the decreased levels of the Th2 cytokine IL-4 in TB-derived samples. In conclusion, we found that HS did show immune-modulator properties in both normal and TB environments. Our studies reinforced the possibility that HS could one day be used as an immune-modulating therapeutic agent.
Rashid
Rashid M
RM
Department of Pathology, Loyola University Medical Center, Maywood, IL 60153, USA.
Lee
John M
JM
Fareed
Jawed
J
Young
M Rita I
MR
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000276:immunology; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006497:Heparan Sulfate / Q000737:chemistry / Q000494:pharmacology*; D007155:Immunologic Factors / Q000737:chemistry / Q000494:pharmacology*; D015847:Interleukin-4 / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
D003208:Concanavalin A; D016207:Cytokines; D006497:Heparan Sulfate; D007155:Immunologic Factors; D015847:Interleukin-4