Modulation of the Tumor Immune Response by Interleukin 1 in the C57bl/6 Murine Model (1986)

aOOTER I '!he primary qoal of this dissertatiai research has been to determine the potential role of interleukin 1 (IL-1) in the development of protective inm.me responses to an experimental lyitplana.'!his biological response ll'Odifier (BRM) is considered for study because of its many known intmunoregulatory roles (64,78), incl~ the ability to augment the inm.me response in defined antigenic systems (285, 312).However, no previous reports have den:>nstrated a direct role for IL-1 in the develcpnent of inmmity to experimental neoplasia.'!he experimental tunw:>r JOOde1 enployed in this study is the Eir4 lyzrphana which is syn_;eneic in C57Bl/6 mice ani results in high llk)rtality (39,100).In this system, mice can be protected f:ran a nonnally fatal dose of the weakly inummogenic Eir4 lynphama (101) by local administration of Cocynebacterium paryum ( 183) However, these animals show no deronstrable tun:>r imrm.mitysince they will succumb to a secoIXl challen;re of the tunw:>r.It has been the p.irpose of this study to determine whether administratiai of IL-1 can enhance anima1 survival or augment the developnent of imrm.mity to the Eir4 lyitpnna.'!he remaining objective of this :research was to assess the cx:rapartments of the imnnme system which may be m::xiul.atedby IL-1 leadin:j to the establishment of tunw:>r imrm.mity.'Ib accomplish this qoal, in vitro analysis of splenic ani lymphatic tissues of treated anilnal.shas been perfonned to assess a possible mechanism( s) by which IL-1 2 may m::xiulate the imm..me response to the Eir-4 lynphana.Several inum.mecorrelates likely to be associated with the developnent of ttnoor immunity ani, therefore, urmr scrutiny in this project, were Eir-4 ttnoor specific cytotoxic T cells, natural killer cells {NK) , ani hunmal antibody response to the Eir-4 lynphana.Also, possible m::xiulation by IL-1 of lyqiloid pcp.1].ations ani their proliferative responsiveness to the Eir-4 lynphana were investigated.All of these inmm:>logical parameters have been reported by other investigators to be augmented by IL-1 am may urmrlie the mechanism by which IL-1 leads to the augmentatioo of turoor imnamity in the Eir-4:C57Bl/6 experimental no:lel. CHAPI'ERII A. Adjuvant Effects of Coeynebacterium paryum over the last twenty-five years, a wide variety of immunostimulants have been shown to effect the growth of synJeneic transplantable tunm's in mice.startirg in the early 19608 with zyioosan (yeast cell walls) (233) arxi Bacillus calmette-Guerin (ED;) (231), this list of inm.mostimul.antshas been exparxied to inclu:ie viable bacteria, bacterial by-products, nonviable bacteria arxi chemically defined ~ (17).'!he first Wication that ~ paryum would be<xme an :i.nportant research tool as an .illm.mological stinulant was dena1strated by Halpern et al. in 1964, when they fa:all c. paryum to be a potent stinulator of the reticulo-emothel.ialsystem ( 109) Many investigators have since verified these observations (123,243,286,294) with c. parvum treated mice showinJ increases in liver arxi spleen weights (5,109,188,197,228) as well as an increased ability to clear intravenously injected cartx>n.c. parvum has been shown to exert adjuvant effects on antibody production, in:iuction of delayed type hypersensitivity (5,25,223), arxi may be satisfactorily substituted for the mycobacterial canponent of F.reurd's cx:arplete adjuvant {223).c. parvum treatment enhances protection against protozoal (226) , viral ( 143) arxi bacterial infection (3) , as well graft-versus-host disease (122).'!here is abumant evidence to Wicate these effects are