Table 3.
Impact of Muscarinic Receptor Antagonists on the Inflammatory Cellular Response Induced by Different Pro-Inflammatory Stimuli in Laboratory Animals. Statistically Significant Results with a P<0.05 are Reported in the Table
| Investigated Treatment | Pro-Inflammatory Stimulus | Investigated Outcomes in the in vivo Studies on Laboratory Animals | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Total Inflammatory Cell Count | Eosinophils | Macrophages | Neutrophils | Lymphocytes | Monocytes | Basophils | Total Protein Amount | Lung Inflammatory Score | ||
| TIO inh. | OVA | BALf:↓36,44* in advanced-age mice,39 chronic challenge,40 acute and chronic challenge;22 ↑ acute challenge;40≈35,41,42 |
BALf: ↓ in advanced-age mice,39 acute onset and relapse of allergic asthma,36,38* acute challenge,22 chronic challenge;22,40 ↑ acute challenge;40≈35,41–43*. Lung: ↓ in submucosal cartilaginous airways,41 acute onset and relapse of allergic asthma;36,38* ≈ in submucosal and adventitia of non-cartilaginous airways and adventitia of cartilaginous airways,41 total and nerve-associated eosinophils43* |
BALf: ↑ acute challenge;40 ↓ acute challenge,22 chronic challenge;22,40≈35,36,41–43*, acute onset of allergic asthma38* | BALf: ↓ in advanced-age mice;39≈35,41–43*, acute challenge,40 chronic challenge,40 acute onset of allergic asthma38* | BALf: ↓ chronic challenge,22,40 acute onset and relapse of allergic asthma38*;≈35,36,39,41,43*, acute challenge22,40 | / | / | / | Lung: ↓ acute onset and relapse of allergic asthma35,38 |
| OVA + exposure to PM | BALf:↓37 | BALf:↓37 | BALf:↓37 | BALf:↓37 | BALf:↓37 | / | / | / | / | |
| CS | BALf:↓28–31 Lung:↓28,31 Serum:≈31 |
BALf:↓31 Serum:≈31 |
BALf:↓28,31≈29 | BALf:↓28–30≈31 Serum:≈31 |
BALf:↓28,29≈31 Serum:≈31 |
BALf:≈30 Serum:≈31 |
Serum:≈31 | Serum:≈31 | Lung:↓28,31 | |
| CS + H1N1 infection | BALf:↓27 | / | BALf:↓27 | BALf:↓27 | / | / | / | / | / | |
| CS + RSV infection | / | / | BALf:≈27 | BALf:↓27 | / | / | / | / | / | |
| OD | BALf:≈34* | BALf:≈34* | BALf:≈34* | BALf:≈34* | BALf:≈34* | / | / | / | / | |
| House dust mite extract | BALf:≈33* | BALf:≈33* | / | / | / | / | / | / | Lung:↓33* | |
| RB | BALf: ↓ 40%IRB, 60%ERB, and 40%/60%CRB;45 ≈ 50%IRB45 | / | BALf: ↓ 40%IRB and 40%/60%CRB;45 ≈ 50%IRB and 60%ERB45 | BALf: ↓ 40%IRB 50%IRB, 60%ERB, and 40%/60%CRB45 | / | / | / | BALf: ↓ 40%IRB and 40%/60%CRB;45 ≈ 50%IRB and 60%ERB45 | / | |
| CdCl2 | BALf:↓47 | / | BALf:≈47 Lung: ↓ in alveoli, peri-bronchial regions, and parenchyma.47 |
BALf:↓47 Lung: ↓ in alveoli, peri-bronchial regions, and parenchyma47 |
/ | / | / | BALf:↓47 | Lung:↓47 | |
| LPS | BALf:≈30 | / | / | BALf:↓30 Lung: ↓ in cartilaginous, non-cartilaginous airways and parenchyma32 |
/ | BALf:≈30 | / | / | / | |
| Acidic solution | BALf:↓46 Lung:↓46 |
/ | BALf:↓46 | BALf:↓46 | BALf:↓46 | / | / | / | / | |
| BCQB inh. | CS | BALf:↓28 Lung:↓28 |
/ | BALf:↓28 | BALf:↓28 Lung:↓28 |
BALf:≈28 | / | / | / | Lung:↓28 |
| OVA | BALf:↓36 | BALf:↓36 Lung:↓36 Nasal mucosa:↓50* |
BALf:↓36 | / | BALf:≈36 | / | / | / | / | |
| GLY syst. | CS | BALf:↓25 | / | BALf:↓25 | BALf:↓25 | BALf:↓25 | / | / | BALf:↓25 | Lung:↓25 |
| GLY inh. | CS | BALf:↓29 | / | BALf:↓29 Lung: ↓ in alveolar spaces29 |
BALf:↓29 Lung: ↓ in alveolar spaces29 |
BALf:≈29 | / | / | / | / |
| V0162 inh. | OVA | BALf:↓44* | / | / | / | / | / | / | / | / |
| IB inh. | OVA | / | Nasal mucosa:↓50* | / | / | / | / | / | / | / |
| CdCl2 | BALf: ↓ acute challenge;52≈51 chronic challenge52 | / | BALf:≈51 acute and chronic challenge52 | BALf:↓51 acute challenge;52 ≈ chronic challenge52 | / | / | / | BALf: ≈ chronic challenge52 | Lung:↓51 | |
| ACL inh. | CS | / | Lung: ≈ in alveolar septa and airways49 | Lung: ≈ in alveolar septa and airways49 | Lung: ↓ in alveolar septa49 | / | / | / | / | / |
| Af extract | / | BALf:↓48 | BALf:≈48 | BALf:≈48 | BALf:≈48 | / | / | BALf:↓48 | / | |
| 4-DAMP syst. | CS | BALf:↓53 | / | BALf:↓53 | BALf:↓53 | BALf:↓53 | / | / | / | / |
| LPS | BALf:↓26 | / | / | BALf:↓26 | / | / | / | / | / | |
| 4-DAMP inh. | PPE | BALf:≈54* | / | / | BALf:≈54* | / | / | / | / | / |
| Mepenzolate bromide inh. | PPE | BALf:↓54 | / | / | BALf:↓54 | / | / | / | / | / |
| CS | Lung:↓54* | / | Lung: ↓ in alveoli54* | Lung:↓54* | / | / | / | / | / | |
| Anisodamine syst. | OVA | BALf:↓55 Lung: ↓ in peribronchial and perivascular regions54 |
BALf:↓55 Lung: ↓ in airway walls55 |
/ | / | / | / | / | / | / |
Note: *Intranasal or intratracheal instillation.
Abbreviations: ACL, aclidinium; Af, Aspergillus fumigatus; BALf, bronchoalveolar lavage fluid; BCQB, bencycloquidium bromide; CdCl2, cadmium chloride; COPD, chronic obstructive pulmonary disease; CRB, combined resistive breathing; CS, cigarette smoke; ERB, expiratory resistive breathing; GLY, glycopyrronium; H1N1, influenza virus A/PR/8/34; IB, ipratropium bromide; IFN, interferon; IL, interleukin; IRB, inspiratory resistive breathing; KC, keratinocyte-derived chemokine; LPS, lipopolysaccharide; MAC-1, macrophage-1 antigen; MCP, monocyte chemoattractant protein; MIP, macrophage inflammatory protein; MMP, matrix metalloproteinase; NA, not available; NLF, nasal lavage fluid; OVA, ovalbumin; PDCD5, programmed cell death protein 5; PM, particulate matter; RB, resistive breathing; ROA, route of administration; RSV, respiratory syncytial virus; TGF- β1, tumor growth factor-beta 1; TIMP, tissue inhibitor of metalloproteinase; TIO, tiotropium bromide or tiotropium bromide hydrate; TNF-α, tumor necrosis factor-alpha; 4-DAMP, 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide.