Experimental Insights on the Use of Secukinumab and Magnolol in Acute Respiratory Diseases in Mice

Abstract

This study investigates the combined treatment of secukinumab (SECU) and magnolol (MAGN) in a mouse model of LPS-induced ALI overlapped with allergic pulmonary inflammation, aiming to better understand the mechanism behind this pathology and to assess the therapeutic potential of this novel approach in addressing the severity of ALI. The combined treatment reveals intricate immunomodulatory effects. Both treatments inhibit IL-17 and promote M2 macrophage polarization, which enhances anti-inflammatory cytokine production such as IL-4, IL-5, IL-10, and IL-13, crucial for lung repair and inflammation resolution. However, the combination treatment exacerbates allergic responses and increases OVA-specific IgE, potentially worsening ALI outcomes. MAGN pretreatment alone demonstrates higher potency in reducing neutrophils and enhancing IFN-γ, suggesting its potential in mitigating severe asthma symptoms and modulating immune responses. The study highlights the need for careful consideration in therapeutic applications due to the combination treatment's inability to reduce IL-6 and its potential to exacerbate allergic inflammation. Elevated IL-6 levels correlate with worsened oxygenation and increased mortality in ALI patients, underscoring its critical role in disease severity. These findings offer valuable insights for the advancement of precision medicine within the realm of respiratory illnesses, emphasizing the importance of tailored therapeutic strategies.

Keywords: acute lung injury; allergic diseases; asthma; magnolol; precision medicine; secukinumab.

Figure 1

Magnolol chemical structure (https://www.chemspider.com/Chemical-Structure.65251.html, accessed on 21 May 2024).

Figure 2

The procedures’ timeline scheme.

Figure 3

IgE concentration in serum (ng/mL). Values are expressed as mean ± standard error; n = 5. OVA + LPS: positive disease control group; OVA + LPS + MAGN: magnolol-treated group; OVA + LPS + SECU: secukinumab-treated group; OVA + LPS + MAGN + SECU: combined magnolol- and secukinumab-treated group. Red lines: mean ± SE; black dots: individual data.

Figure 4

Differential cell count, optical microscopy: (a) OVA + LPS group: cellularity, ×10 dry objective; (b) OVA + LPS group: neutrophils, hypersegmented neutrophil (arrow), ×100 immersion objective; (c) OVA + LPS + SECU group: neutrophils and an eosinophil (arrow), ×100 immersion objective; (d) OVA + LPS + SECU group: binucleated alveolar macrophage (arrow) and neutrophils, ×100 immersion objective; (e) OVA + LPS + MAGN group: binucleated alveolar macrophage, neutrophils and an eosinophil (arrow), ×40 dry objective; (f) OVA + LPS + MAGN group: eosinophil, ×100 immersion objective; (g) OVA + LPS + MAGN + SECU group: cellularity, ×10 dry objective; (h) OVA + LPS + MAGN + SECU group: neutrophil and lymphocyte, ×100 immersion objective.

Figure 5

Graphical illustration of the differential cell counts expressed in percentages for (a) macrophages, (b) neutrophils, (c) lymphocytes, and (d) eosinophils. Values are expressed as mean ± standard error; n = 5. * p < 0.05 vs. OVA + LPS group; # p < 0.05 vs. OVA + LPS + SECU group; ‡ p < 0.05 vs. OVA + LPS + MAGN + SECU group; as determined by one-way ANOVA, followed by the Holm–Šidák method for multiple comparisons. OVA + LPS: positive disease control group; OVA + LPS + MAGN: magnolol-treated group; OVA + LPS + SECU: secukinumab-treated group; OVA + LPS + MAGN + SECU: combined magnolol- and secukinumab-treated group. Red lines: mean ± SE; black dots: individual data.

Figure 6

Cytokine concentration (pg/mL) in BALF: (a) TNF-α, (b) VEGF, (c) IL-4, (d) IL-5, (e) IL-6, (f) IL-13, (g) IL-17, and (h) IFN-γ. Values are expressed as mean ± standard error; n = 5. * p < 0.05 vs. OVA + LPS group; # p < 0.05 vs. OVA + LPS + SECU group; ‡ p < 0.05 vs. OVA + LPS + MAGN + SECU group; as determined by one-way ANOVA, followed by the Holm–Šidák method for multiple comparisons. OVA + LPS: positive disease control group; OVA + LPS + MAGN: magnolol-treated group; OVA + LPS + SECU: secukinumab-treated group; OVA + LPS + MAGN + SECU: combined magnolol- and secukinumab-treated group. Red lines: mean ± SE; black dots: individual data.

Figure 7

Cytokine concentration (pg/mL) in lung tissue homogenate: (a) TNF-α, (b) VEGF, (c) IL-4, (d) IL-5, (e) IL-6, (f) IL-13, (g) IL-17, and (h) IFN-γ. Values are expressed as mean ± standard error; n = 6. * p < 0.05 vs. OVA + LPS group; # p < 0.05 vs. OVA + LPS + SECU group; as determined by one-way ANOVA, followed by the Holm–Šidák method for multiple comparisons. OVA + LPS: control group—positive for disease; OVA + LPS + MAGN: magnolol-treated group; OVA + LPS + SECU: secukinumab-treated group; OVA + LPS + MAGN + SECU: combined magnolol- and secukinumab-treated group. Red lines: mean ± SE; black dots: individual data.

Figure 8

Representative HE- and PAS-stained tissue sections of lungs and bronchia from mice in ovalbumin-induced asthma exacerbated with LPS administration. Original magnification for HE: ×40 or ×100, for PAS: ×1000. SAL: normal control group; OVA + LPS: positive disease control group; OVA + LPS + MAGN: magnolol-treated group; OVA + LPS + SECU: secukinumab-treated group; OVA + LPS + MAGN + SECU: combined magnolol- and secukinumab-treated group.