Induction of popliteal lymph node enlargement and antibody production in the mouse by pyridylallylamines related to zimeldine.
The role of the para-brominated phenyl ring of the allylamine antidepressant drug, zimeldine, in its immunomodulating activity was studied by comparing local lymph node responses of mice to analogues with various phenyl ring substituents. The compounds (1.0 mg) were injected into the hind footpad and weight and cell number of the popliteal lymph node (PLN) and antibody production by PLN cells were determined 7 days later. Zimeldine and the para-trimethylsilylated and ortho-para-chlorinated compounds induced a marked PLN weight gain in C57BL/6 mice. The para-chlorinated and meta-brominated analogues were significantly less effective, while the para-fluorinated and the unsubstituted analogue failed to trigger PLN weight gain. The same range of potency of the compounds was seen when increases of PLN cell number in BALB/c mice and increases of IgM production by a fixed number of BALB/c PLN cells were determined. The IgG production on a per cell basis was not increased by the fluorinated and the unsubstituted compounds, while the remaining compounds stimulated the IgG production to a similar extent. Plots of the lipophilicity of the para-substituted compounds against their ability to induce PLN weight and cell gain showed a fair correlation, but induction of antibody formation tended to be counteracted at too high lipophilicity. No correlation between pharmacologic and immunologic activity of the compounds could be found. Data indicate that lipophilicity grossly favours PLN enlargement, but the divergent responses to the equilipophilic 3- and 4-brominated compounds, suggest conformational restraints as well.(ABSTRACT TRUNCATED AT 250 WORDS)
Thomas
C
C
Research Institute of Toxicology, Section Immunotoxicology, University of Utrecht, The Netherlands.
Lippe
W
W
Högberg
T
T
Seinen
W
W
Bloksma
N
N
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000917:Antibody Formation / Q000187:drug effects*; D002452:Cell Count / Q000187:drug effects; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007717:Knee; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D013329:Structure-Activity Relationship; D015031:Zimeldine / Q000031:analogs & derivatives / Q000494:pharmacology
D000906:Antibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015031:Zimeldine