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Nedocromil sodium modulates the function of long-term rat peritoneal mast cell cultures
M Shalit1, N Riesel-Yaron, F Levi-Schaffer
1Department of Medicine, Hadassah University Hospital, Jerusalem, Israel.
Abstract:
Long-term rat peritoneal mast cell (MC) cultures consisting of MC co-cultured with 3T3 fibroblasts (MC/3T3) were employed to study the effects of repeated and prolonged incubation with nedocromil sodium (10(-3) and 10(-5) M) on MC activation. When nedocromil sodium was added simultaneously with compound 48/80 to MC/3T3 on the first day of the experiment, it inhibited histamine release to the same extent as when added to the cultures a week later upon rechallenge. In other experiments activated MC/3T3 were incubated with nedocromil sodium for a week and on the last day of the experiment fresh nedocromil sodium was added simultaneously with compound 48/80. Under these conditions the drug was as potent in inhibiting histamine release from the activated MC as it was in cultures incubated for a week with medium alone. In addition, preincubation of naive MC with nedocromil sodium for two days inhibited histamine release from these cells when activated for the first time. Salbutamol (10(-3) and 10(-5) M) exhibited a similar inhibitory effect to nedocromil sodium upon simultaneous incubation with MC/3T3. However, prolonged incubation of salbutamol with MC/3T3 cultures resulted in tachyphylaxis. We conclude that nedocromil sodium is an effective MC stabilizing drug since it similarly inhibits histamine release from both primarily and secondarily challenged MC. Moreover this drug does not lose its efficacy upon prolonged incubation with MC.
Insights
Nedocromil sodium effectively stabilizes mast cells (MC) by inhibiting histamine release upon initial and repeated challenges. Unlike salbutamol, its efficacy is maintained even after prolonged incubation, indicating sustained mast cell stabilization.
Area of Science:
- Immunology
- Pharmacology
Background:
- Mast cells (MC) play a crucial role in allergic responses.
- Understanding mast cell stabilizers is vital for developing anti-allergic therapies.
Purpose of the Study:
- To investigate the long-term effects of nedocromil sodium on mast cell activation.
- To compare the efficacy of nedocromil sodium with salbutamol under prolonged incubation conditions.
Main Methods:
- Utilized long-term rat peritoneal mast cell (MC) cultures co-cultured with 3T3 fibroblasts (MC/3T3).
- Administered nedocromil sodium and compound 48/80 at various time points to assess histamine release.
- Evaluated the impact of prolonged drug incubation and repeated challenges on MC response.
Main Results:
- Nedocromil sodium inhibited histamine release effectively, regardless of whether it was added during initial challenge or rechallenge.
- Prolonged incubation of nedocromil sodium with MC/3T3 cultures did not diminish its inhibitory effect.
- Salbutamol showed initial inhibition but developed tachyphylaxis with prolonged exposure.
Conclusions:
- Nedocromil sodium is a potent mast cell stabilizing drug with sustained efficacy.
- Its ability to inhibit histamine release from both primarily and secondarily challenged mast cells makes it a promising therapeutic agent.