Inhibition of Protein Synthesis by Chloramphenicol

Humoral Antibody Production Following Primary and Secondary immunization in Rabbits Treated with Thiamphenicol and Chloramphenicol

“…Indeed, some of the available experimental evidence regarding CAPH seems to indicate that it acts in quite this manner: it inhibits the proliferation and provokes toxic degeneration of the erythroblasts in man mainly when administered during periods of accelerat ed erythropoiesis, as in vitamin B,2-treated pernicious anemia or during iron therapy of iron deficiency anemias [19,24,28], and it was shown to inhibit in vitro antibody synthesis by lymph node fragments of pre viously immunized rabbits mainly when acting during the early (prolifer ative) phase of the immune response which precedes most of the actual synthesis of antibody [1], The lack of any depressing effect of the 12-day TAPH treatment on the RBC and WBC of group A rabbits concurs to indicate that this drug, like CAPH, does not act on hemopoietic cells proliferating at a normal rate. In fact the failure of TAPH to modify the WBC (except a few cases where neutrophils only were diminished) has already been re ported by other authors [8].…”

“…2 Chloramphenicol has been shown to inhibit protein and antibody synthesis both in vitro -in mammalian cell-free [24,29,30] or cellular [1,11,18,23,24,31] systems -and in vivo in man [7,27] and ani mals [5,10] during primary, sometimes also secondary [1,4,7] immune responses, to prolong skin graft survival [3,24,26,29], to prevent the development of experimental immune nephritis [3,24,27,28] and to cure renal disease of supposed immunological origin in man, parallelly diminishing the serum y-globulin levels [13]. As for thiamphenicol, be sides being a very potent antibiotic [8], it has also proved to have an important immunosuppressive activity: it diminishes antibody production in vitro in cell-free systems [3,24] and in vivo, in man and animals [3,24], prolongs graft survival [12,24,25] and has a favorable effect in patients with lupus glomerulonephritis where it can bring about the dis appearance of the glomerular-bound y-globulin [3,22,25].…”

Humoral Antibody, Plaque, and Rosette Formation in Mice treated with Thiamphenicol and Chloramphenicol

“…It is well established that chloramphenicol and some of its analogues, among which the best known is thiamphenicol2, depress protein synthesis and immune reactions such as active antibody production [1,4,7,10,14,15,19,23,28,30,33,35,36,38], graft rejection [18,19,30,31,35], autoimmune nephritis [4,20,30,33,34], and certain immunologic alter ations associated with systemic lupus erythematosus [4,27,31]. Accord ing to some authors, the underlying mechanism of this activity is sup-posed to be a hampering effect of these compounds on the specific mes senger ribonucleic acid binding to ribosomes, involving an inhibition of immunoglobulin synthesis [2,7,19,25,32,34,36].…”

“…While this theory may account well enough for the phenomena con nected with the suppression of primary antibody production, it can hardly explain why the graft rejection phenomena (in which the synthesis of im munoglobulins plays but a secondary, if any role) are inhibited, while sec ondary immune responses in vivo, although implying active immunoglob ulin synthesis, are less or not influenced by these immuno-inhibitors, at least in animals [4,6,8,30,32,34].…”

“…(b) The same antibiotic in hibited in vivo the immunospecific cell proliferation induced by heterolo gous antigens in mice, but had no effect on the background number of the concerned cells [13]. (c) The 'priming' of mice immunized with diphtheria toxoid was inhibited by chloramphenicol only when this compound was administered during the first 48 h after the antigen injection [6], that is just during the interval when antigen stimulated cells are supposed to pro liferate actively [3], (d) Chloramphenicol determined inhibition of prolif eration and toxic degeneration of erythroblasts in man, mainly when ad ministered during periods of accelerated erythropoiesis, as after a vitamin Bjq treated pernicious anaemia or during iron therapy of iron deficiency anaemias [24,30,34]; it was shown also to inhibit in vitro antibody syn thesis by lymph node fragments of previously immunized animals mainly when acting during the early (proliferative) phase of the immune response preceding most of the actual synthesis of antibody [1], Besides, it is diffi cult to admit that the resistance of the secondary immune response to the immunosuppressive activity of chloramphenicol and thiamphenicol can be accounted for by the existence at that time of active polysomes already formed; indeed, on account of the short life of the messenger ribonucleic acids one must suppose that any secondary rise in the antibody produc tion rate should be preceded by the synthesis of a supplementary amount 100 D ella Bella et at. Humoral Antibody, Plaque, and Rosette of new m-RNA molecules, the binding to ribosomes of which should be prevented, with subsequent impairment of antibody chain formation, if the immunosuppressors acted in this way.…”