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1 We studied the e ect exerted by hr-interleukin-1a (IL-1a) on responsiveness of alveolar macrophages (AM) from naive and sensitized guinea-pigs, through O 2 -. production (by ferricytochrome C reduction), platelet-activating factor (PAF) release (by platelet aggregation), prostaglandin E 2 (PGE 2 ) release (by a radioimmunoassay), and cytosolic phospholipase A 2 (cPLA 2 ) activity (by hydrolysis of radioactive substrate). 2 In naive guinea-pig AM, 0.06 nM hr-IL-1a pretreatment decreased by 65% O 2 -. release stimulated with 10 nM fMLP. In contrast, O 2 -. production was not a ected in sensitized guinea-pig AM.3 O 2 -. release elicited by fMLP stimulation in both cell groups was a ected by PLA 2 inhibitors (10 mM bromophenacyl bromide, BPB or 10 mM methylprednisolone, MP). In contrast, 10 mM arachidonyl tri¯uoromethyl ketone (AACOCF 3 ), a cPLA 2 inhibitor, was ine ective. 4 In naive AM, PAF release was elicited by hr-IL-1a pretreatment and by separate fMLP-stimulation, but when the stimulus was added to hr-IL-1a-pretreated cells inhibition of PAF release was observed. In sensitized AM, PAF release was lower than that found in naive guinea-pig AM in both hr-IL-1a-pretreated and fMLP-stimulated cells. 5 PGE 2 release was una ected by hr-IL-1a pretreatment and it was decreased by fMLP in both naive and sensitized AMs. The latter released less PGE 2 than naive cells in basal conditions and after fMLP treatment. 6 Sensitized AM showed a greater cPLA 2 activity in all experimental conditions in comparison to naive cells. cPLA 2 activity assayed in the cytosolic fraction was found to be enhanced by hr-IL-1a pretreatment and by fMLP stimulation in naive but not in sensitized AM. However, when the stimulus was added to hr-IL-1a-pretreated cells we observed a decrease in cPLA 2 activity in the cytosol and an increase in the membranes, thus suggesting a translocation of enzymatic activity. 7 In conclusion, hr-IL-1a can modulate the responsiveness of AM from naive and sensitized guineapigs, as suggested by changes found in the release of PAF and O 2 -. and in cPLA 2 activity; therefore, sensitization itself may a ect cellular responsiveness.

In sensitized guinea‐pigs, the effects of γ‐aminobutyric acid (GABA) and GABAmimetic drugs have been investigated on tracheal segments contracted by cumulative application of an allergen (ovoalbumin, OA) and on serosal mast cells. The same drugs have also been tested on activation of alveolar macrophages isolated from unsensitized guinea‐pigs. Superfusion with GABA (1–1000 μM) reduced the contraction intensity of tracheal strips. The effect of GABA (100 μM) was not affected by the carrier blockers, nipecotic acid and β‐alanine (300 μM each). It was mimicked by the GABAB agonist (−)−baclofen (100 μM) but not 3‐aminopropanephosphinic acid (100 μM, 3‐APA). The GABAA agonist, isoguvacine (100 μM) did not exert any effect. GABA (10 μM)‐induced inhibition of tracheal contractions was reduced by the GABAB antagonist, 2‐hydroxysaclofen (100 μM, 2‐HS), but not by the GABAA antagonist, bicuculline (30 μM). The reduction in contraction intensity induced by GABA (100 μM) was prevented by a 40 min preincubation of tracheal strips with capsaicin (10 μM), but not tetrodotoxin (TTX, 0.3 μM). The effect of GABA (1000 μM) was absent after preincubation with indomethacin (2.8 μM) but unmodified when nordihydroguaiaretic acid (NDGA, 3.3 μM) was used. Finally, removal of the epithelium prevented the GABA effect. Anaphylactic histamine release from serosal mast cells isolated from sensitized animals was not affected either by GABA (10–1000 μM) or the selective receptor agonists (−)−baclofen (0.1–1000 μM) and isoguvacine (10–1000 μM). The release of platelet‐activating factor (PAF) from alveolar macrophages stimulated by formyl‐Met‐Leu‐Phe (FMLP; 1 μM) was modified neither by GABA (100 μM) nor by (−)−baclofen (100 μM). In conclusion, these data show that GABA can inhibit allergic phenomena in the guinea‐pig airways through activation of GABAB receptors. An involvement of neuropeptidergic sensory structures is suggested but a role for epithelial cells and arachidonate metabolites is not definitely proved.

Salmeterol (1 nM-100 microM) showed an inhibitory action on anaphylactic histamine release from mast cells, isolated from pleural and peritoneal cavities of actively sensitized guinea-pigs and stimulated by incubation with allergen. The effect is concentration-dependent and is reduced by the beta-adrenoceptor antagonist propranolol (1 microM). This study supports the hypothesis of an anti-inflammatory property of salmeterol, which concerns cells involved in the early phases of asthma.